Category: 3. Business

Neoadjuvant treatment with fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) followed by paclitaxel, trastuzumab (Herceptin), and pertuzumab (Perjeta; THP) led to an improvement in pathologic complete response (pCR) rate compared with dose-dense doxorubicin and cyclophosphamide plus THP (ddAC-THP) in patients with high-risk, HER2-positive early breast cancer, according to data from the phase 3 DESTINY-Breast11 trial (NCT05113251).¹

Findings presented at the 2025 ESMO Congress demonstrated that patients treated with T-DXd followed by THP (n = 321) experienced a pCR rate of 67.3% compared with 56.3% for those given ddAC-THP (n = 320; difference, 11.2%; 95% CI, 4.0%-18.3%; P = .003). Notably, the pCR benefit was observed in the hormone receptor–positive population, where the pCR rate was 61.4% in the T-DXd arm (n = 236) vs 52.3% in the ddAC-THP arm (n = 235; difference, 9.1%; 95% CI, 0.2%-17.9%), as well as the hormone receptor–negative population, where the respective pCR rates for the T-DXd arm (n = 83) and ddAC-THP arm (n = 85) were 83.1% and 67.1% (difference, 16.1%; 95% CI, 3.0%-28.8%).

“DESTINY-Breast11 showed the highest reported pCR rate in HER2-positive early breast cancer for a registrational study in the neoadjuvant setting, despite—if you want to do cross-trial comparisons—a high prevalence of hormone receptor–positive disease and a high-risk population,” lead study author Nadia Harbeck, MD, PhD, said in a presentation of the data.

DestinyBreast-11 Highlights

• Neoadjuvant T-DXd followed by THP generated a pCR benefit vs ddAC-THP in patients with high-risk, HER2-positive early breast cancer, with the experimental regimen generating an 11.2% pCR rate improvement.

• The FDA is reviewing a supplemental biologics license application seeking the approval of neoadjuvant T-DXd plus THP in this patient population.

• The T-DXd monotherapy arm in DESTINY-Breast11 was closed early following a recommendation from the trial’s independent data monitoring committee.

Harbeck is director of the Breast Center and chair for Conservative Oncology at the Department of OB&GYN at LMU University Hospital in Munich, Germany.

How Was the DESTINY-Breast11 Trial Designed?

Harbeck noted that current neoadjuvant standard-of-care (SOC) regimens for HER2-positive early breast cancer have remained unchanged for more than a decade. As such, investigators sought to evaluate T-DXd–based treatment in this population with the goal of improving efficacy and safety vs the current SOC.

The randomized, global, multicenter, open-label study enrolled patients with previously untreated HER2-positive early breast cancer who had high-risk disease, defined as ≥cT3 and N0-3 or cT0-4 and N1-3; or inflammatory breast cancer. Patients were allowed to enroll, irrespective of hormone receptor status.

Patients were randomly assigned in a 1:1:1 fashion to receive T-DXd followed by THP; ddAC-THP; or T-DXd alone, followed by surgery in all arms. In the first arm, patients received 4 cycles of T-DXd followed by 4 cycles of THP. In the second, ddAC was administered for 4 cycles, followed by 4 cycles of THP. In the final arm, patients received T-DXd alone for 8 cycles.

Notably, the T-DXd monotherapy arm was closed in March 2024, following a recommendation from the study’s independent data monitoring committee.

After surgery, study protocols called for the following treatments, irrespective of arm:

• pCR: radiotherapy and concomitant trastuzumab with or without pertuzumab for up to 1 year
• Non-pCR: radiotherapy and ado-trastuzumab emtansine (Kadcyla) for up to 14 cycles
• Hormone receptor–positive disease: endocrine therapy

The study’s primary end point was pCR rate (ypT0/Tis ypN0) per blinded independent central review (BICR) assessment. Secondary end points included BICR-assessed pCR rate (ypT0 ypN0), event-free survival (EFS), safety, pharmacokinetics, invasive disease-free survival, overall survival, and health-related quality of life. Residual cancer burden (RCB) was an additional outcome measured during the study.

At data cutoff, 16.9% of patients in the T-DXd plus THP arm discontinued a study drug, including T-DXd (2.8%), paclitaxel (14.4%), trastuzumab (2.2%), and pertuzumab (2.2%); 97.2% of patients in this arm proceeded to surgery. In the ddAC-THP arm, 13.8% of patients had discontinued any study treatment, including AC (2.9%), paclitaxel (12.0%), trastuzumab (3.0%), and pertuzumab (3.7%); 93.8% of patients in this arm underwent surgery. In the T-DXd monotherapy arm (n = 286), 18.4% of patients discontinued study treatment, and 95.8% underwent surgery.

Regarding post-neoadjuvant treatments, 99.1% of evaluable patients in the T-DXd arm who achieved a pCR (n = 226) underwent any adjuvant therapy, comprising any cytotoxic chemotherapy regimen (5.8%), any T-DM1–containing regimen (1.8%), and any trastuzumab-containing regimen (94.2%). In the ddAC-THP, 98.4% of patients who achieved a pCR (n = 190) underwent any adjuvant therapy, including any cytotoxic chemotherapy regimen (5.8%), any T-DM1–containing regimen (2.1%), and any trastuzumab-containing regimen (91.6%).

For patients who did not achieve a pCR, any adjuvant therapy was administered to 89.5% of patients in the T-DXd plus THP arm (n = 95) and 82.3% of patients in the ddAC-THP arm (n = 130). In the experimental group, adjuvant therapies included any cytotoxic chemotherapy regimen (10.5%), any T-DM1–containing regimen (52.6%), and any trastuzumab-containing regimen (38.9%). These respective rates were 9.2%, 56.9%, and 26.2% in the control group.

In the T-DXd plus THP and ddAC-THP arms, the median age was 50 years (range, 25-82) and 50 years (range, 23-79), respectively. All patients in both arms were female. The highest proportion of patients in each arm was from Asia (T-DXd plus THP, 47.4%; ddAC-THP, 47.5%) and were Asian (49.8%; 49.1%). Most patients had an ECOG performance status of 0 (86.6%; 87.5%), had immunohistochemistry 3+ HER2-positive disease (87.2%; 88.4%), had cT0-2 tumors (54.8%; 58.8%), and had positive lymph nodes (89.4%; 87.8%).

What Were the Other Efficacy Outcomes for T-DXd Plus THP vs ddAC-THP?

Findings also showed that 81.3% of patients in the T-DXd plus THP arm had no RCB (RCB-0) or minimal RCB (RCB-1) in resected breast or lymph node tissue compared with 69.1% in the ddAC-THP arm (difference, 12.2%). In the hormone receptor–positive population, the RCB-0 plus RCB-1 rates were 78.0% for T-DXd plus THP vs 64.7% for ddAC-THP; these respective rates were 90.4% and 81.2% in the hormone receptor–negative population.

Investigators also reported an EFS trend favoring T-DXd plus THP, with data at 4.5% maturity (HR, 0.56; 95% CI, 0.26-1.17). Maturity for the data cutoff of the trial’s final analysis is predicted at approximately 10%. The 24-month EFS rates were 96.9% (95% CI, 93.5%-98.6%) in the T-DXd plus THP arm vs 93.1% (95% CI, 88.7%-95.8%) in the ddAC-THP arm.

What Is the Safety Profile of T-DXd Plus THP?

Any-grade adverse effects (AEs) occurred in 98.1% of patients in the T-DXd plus THP arm compared with 98.7% of patients in the ddAC-THP arm. The respective rates of grade 3 or higher AEs were 37.5% and 55.8%. Any-grade serious AEs were reported in 10.6% and 20.2% of patients, respectively.

In the T-DXd plus THP arm, AEs led to dose any dose reduction, any drug interruption, and any treatment discontinuation in 18.1%, 37.8%, and 14.1% of patients, respectively. In the ddAC-THP group, these rates were 19.2%, 54.5%, and 9.9%, respectively. AEs led to death in 0.6% of patients in both arms. AEs led to delays in surgery in 3.4% of patients in the experimental arm vs 2.6% of patients in the control arm.

Regarding AEs of special interest, any-grade drug-related adjudicated interstitial lung disease (ILD) was 4.4% in the T-DXd plus THP arm vs 5.1% in the ddAC-THP arm. The rates of grade 3 or higher ILD were 0.6% and 1.9%, respectively. Grade 5 ILD occurred in 1 patient (0.3%) in both groups. Any-grade left ventricular dysfunction occurred in 1.3% of patients in the experimental arm vs 6.1% of patients in the control arm. The rates of grade 3 or higher left ventricular dysfunction were 0.3% and 1.9%, respectively, although no grade 5 events were reported in either group.

Any-grade treatment-emergent AEs reported in at least 20% of patients in either arm included nausea (T-DXd plus THP, 64.7%; ddAC-THP, 51.6%), diarrhea (58.8%; 54.2%), alopecia (47.5%; 49.0%), fatigue (41.3%; 54.8%), increased transaminase levels (34.4%; 33.7%), neutropenia (29.1%; 44.2%), constipation (29.1%; 24.4%), vomiting (28.8%; 21.2%), peripheral neuropathy (25.9%; 20.8%), anemia (22.8%; 49.7%), stomatitis (18.4%; 27.9%), and leukopenia (17.2%; 23.4%).

What Data Were Reported for T-DXd Monotherapy in HER2+ Early Breast Cancer?

When the T-DXd monotherapy arm, patients were allowed to remain on therapy or immediately switch to local SOC. If patients switched therapy, they were classified as having a non-pCR.

Findings from the monotherapy arm showed that patients (n = 286) achieved a pCR rate of 43.0% at the primary analysis and 51.4% at a prespecified supplementary analysis. EFS data were similar between T-DXd monotherapy and ddAC-THP (HR, 0.82; 95% CI, 0.41-1.62), and the 24-month EFS rate in the T-DXd monotherapy group was 94.4% (95% CI, 90.5%-98.7%).

Regarding safety, 97.5% of patients treated with T-DXd alone (n = 283) experienced any-grade AEs, 22.6% had grade 3 or higher AEs, and 10.2% had any-grade serious AEs. AEs led to dose reduction, drug interruption, and treatment discontinuation in 6.7%, 18.0%, and 7.8% of patients, respectively. One patient (0.4%) experienced an AE that led to death. AEs led to surgical delay in 6.4% of patients.

The rate of any-grade, drug-related adjudicated ILD was 4.9% in the T-DXd monotherapy arm, although all instances were grade 1 or 2. Left ventricular dysfunction occurred in 0.7% of patients, all at grade 1 or 2.

What’s Next for T-DXd Plus THP?

Based on data from DESTINY-Breast11, the FDA accepted a supplemental biologics license application seeking the approval of neoadjuvant T-DXd followed THP for the treatment of adult patients with high-risk, HER2-positive (IHC 3+ or in situ hybridization–positive), stage II/III breast cancer.²

The FDA has assigned a target action date of May 18, 2026, under the Prescription Drug User Fee Act.

“DESTINY-Breast11 results support T-DXd [plus] THP as a more effective and less toxic neoadjuvant treatment compared with ddAC-THP, and it may become the preferred regimen for patients with high-risk, HER2-positive early breast cancer,” Harbeck concluded in her presentation.¹

Disclosures: Harbeck reported receiving honoraria from AstraZeneca, Daiichi Sankyo, Gilead, Lilly, Menarini Stemline, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Viatris, and Zuellig Pharma; serving as a consultant or advisor for Exact Sciences, Gilead, Pfizer, Roche, and Sandoz; having an institutional site contract with AstraZeneca; serving as a data safety monitoring board or advisory board member for Gilead, IQVIA, and Roche; and having ownership interested in the West German Study Group.

References

1. Harbeck N, Modi S, Pusztai L, et al. DESTINY-Breast11: neoadjuvant trastuzumab deruxtecan alone (T-DXd) or followed by paclitaxel + trastuzumab + pertuzumab (T-DXd-THP) vs SOC for high-risk HER2+ early breast cancer (eBC). Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract 291O.
2. Enhertu followed by THP supplemental biologics license application accepted in the U.S. for patients with high-risk HER2 positive early-stage breast cancer prior to surgery. News release. Daiichi Sankyo. October 1, 2025. Accessed October 18, 2025. https://www.daiichisankyo.com/files/news/pressrelease/pdf/202510/20251001_E.pdf

Decades of clinical research has led to the discovery of key biomarkers, development of novel agents, and the subsequent improvement in patient survival outcomes.

At the European Society for Medical Oncology 2025 Congress, Jürgen Wolf, MD, medical director at the Center for Integrated Oncology, and chair of the Lung Cancer Program at Center for Integrated Oncology at the University Hospital of Cologne, shared key updates in non-small cell lung cancer (NSCLC) treatment. He discussed novel drugs and emphasized the crucial role of molecular diagnostics in guiding treatment decisions to ensure every patient receives the right therapy at the right time.

Lung cancer represents the second most common cancer in the United States, with over 260,000 new cases in 2025. NSCLC is the most prevalent type of lung cancer, representing roughly 80% to 85% of cases. Pivotal advancements in drug development have significantly improved survival rates for patients over the past 40 years—12.4% in the mid-1970s to 26.7% by 2020. Various investigational and FDA approved agents are responsible—from tyrosine kinase inhibitors (TKIs) to other targeted therapies.^1-3

However, mutations present continued obstacles to optimal outcomes. In NSCLC, there are various mutations not limited to EGFR, ALK fusion, ROS1, BRAF V600E, HER2, and KRAS. Wolf discussed the benefit of molecular diagnostic testing even prior to initiation of therapy for NSCLC. Liquid biopsy has a high specificity but limited sensitivity. He establishes tissue biopsy as the continuing gold standard for molecular diagnostics.⁴

“Molecular diagnostics remains the foundation of personalized care in [NSCLC],” Wolf said. “Comprehensive testing before first line therapy should include all guideline recommended markers. RNA next-generation sequencing is essential for sensitive fusion detection.”⁴

EGFR

EGFR mutations are the most common in NSCLC—representing 10% to 15% of lung adenocarcinomas. It is more prevalent and in nonsmokers, women, and Asian populations, with exon 19 deletion and exon 21 L858R being the most frequent mutations. In the adjuvant setting following surgery, osimertinib (Tagrisso; AstraZeneca), a TKI, is the standard of care with proven overall survival (OS) benefit in resected early-stage NSCLC.^4,5

Osimertinib’s successfully secured multiple FDA approvals, supported by data showing its efficacy in adjuvant and neoadjuvant settings. The first approval was supported by data from the randomized, double-blind, placebo-controlled ADAURA trial (NCT02511106). Four years later, the FDA granted osimertinib another approval in the adjuvant setting supported by data from the double blind, randomized, placebo-controlled LAURA trial (NCT03521154).^6-9

Wolf highlights the FLAURA-2 and MARIPOSA trials (NCT04035486; NCT04487080), which is exploring osimertinib as a monotherapy. Both trials had a primary end point of progression-free survival (PFS) and OS and showed osimertinib’s superiority over other available TKIs. OS was favorable and similar between both trials at 60% vs 51% (for combination vs monotherapy) in MARIPOSA and 63% vs 51% (for combination vs monotherapy) in FLAURA-2. The researchers report an approximate 10 to 12 months improvement with a hazard ratio of 0.75 for both trials.^4,10,11

Compared with combination therapies, osimertinib as a monotherapy was associated with less toxicity. Combination therapies yielded more severe adverse events (AEs) and higher rates of treatment interruption. Patients in FLAURA-2 experienced chemotherapy-associated side effects, while MARIPOSA patients had painful infusion reactions such as rash and pulmonary embolism.⁴

“However, this improved efficacy comes at the cost… combination therapies are significantly more toxic than monotherapy,” explained Wolf. “But I think it’s fair enough to say that toxicity management has improved substantially with prophylactic skincare, subcutaneous formulation and anti-coagulation. Nevertheless, they remain challenging in clinical routine.”⁴

However, osimertinib shows additional efficacy across as a neoadjuvant treatment. Wolf highlights the NEOADURA trial (NCT04351555), a randomized phase 2 trial comparing osimertinib to placebo. The primary end point was major pathological response, which showed a clear advantage for osimertinib.^4,12

“I think this is really an attractive option for these patients, and should be considered and discussed in the tumor growth.”⁴

ALK Fusion

ALK fusions are detected in approximately 1% to 4% of lung cancers, most often in adenocarcinomas. These alterations tend to occur in younger patients and those with minimal smoking history. Alectinib (Alecensa; Genentech) is the current standard-of-care therapy for ALK-positive NSCLC and received FDA approval in 2024 for adjuvant use following tumor resection.^2,4

Wolf highlights other approved agents in this setting including lorlatinib (Lorbrena; Pfizer Inc) and crizotinib (Xalkori; Pfizer), which were compared head-to-head in the CROWN trial (NCT03052608).^4,13

“Lorlatinib has been tested in a phase 3 study against crizotinib, which has already shown progression-free survival benefits in use,” said Wolf, “and it’s a better drug—65% versus around 40% with the second-generation inhibitors.”⁴

CROWN results showed a 5-year PFS of 60% in lorlatinib with favorable brain activity. In patients without initial brain metastases, the data showed a hazard ratio of 0.05 for central nervous system progression.Permanent discontinuation rates were 11% vs 7%.⁴

“However, there are still a lot of reservations against this drug, and this is based on new side effects, such as hydrochlorist weight gain and, in particular, neurologic AEs,” Wolf explained. “There were also some reservations from patients about stem cell use, but when we look at the permanent discontinuation rates from the trial—11% versus 7%—it’s not necessarily more toxic. There’s a learning curve involved.”⁴

ROS1

ROS1 rearrangements account for 1% to 2% of NSCLC cases with an estimated 10,000 to 15,000 new cases every year around the world. Although relatively uncommon in comparison to other mutations. Patients with ROS1 mutations are younger with a history of light smoking; however, some diagnosed patients have no history of smoking.¹⁴

ROS1 mutated lung cancers exhibit clinical similarities to ALK-rearranged NSCLC, though ROS1, EGFR, and ALK rearrangements are generally mutually exclusive. After exposure to TKIs, a subset of ROS1-positive tumors acquires secondary driver mutations, predominantly in KRAS or EGFR.⁴

“For ROS1 fusions, we have active TKIs approved in the first line—entrectinib (Rozlytrek; Genentech), crizotinib, and epotrectinib (Augtyro; Bristol Myers Squibb)—entering for resistant fusions,” said Wolf. “In this field, we already have a next-generation agent approved now after TKI failure.”⁴

HER2

HER2 mutations are seen across cancer types. In lung cancer, they are rarer than ROS1 and ALK fusions, occurring in approximately 0.2% of patients. Wolf highlights datopotamab deruxtecan-dlnk (Datroway;_Daiichi Sankyo, Inc) and zongertinib (Hernexeos; Boehringer Ingelheim Pharmaceuticals, Inc), which are both FDA approved for treatment of patients with NSCLC as of 2025. D-DXd is approved for adults with locally advanced or metastatic EGFR-mutated NSCLC who received prior EGFR-directed therapy and platinum-based chemotherapy.^4,15

Zongertinib is the most recent approval for adults with unresectable or metastatic nonsquamous NSCLC whose tumors have HER2 mutations based on positive data from the Beamion LUNG-1 trial (NCT04886804).^16,17

Beamion LUNG-1 is an open-label, phase 1 dose escalation trial evaluating zongertinib as a monotherapy in patients with unresectable or metastatic, nonsquamous NSCLC with HER2 TKD mutations. The overall response rate was about 75% (95% CI, 63–83), with 58% experiencing a duration of response of 6 months or longer.¹⁸

KRAS

KRAS G12C mutations represent one of the most significant oncogenic drivers in lung cancer, though therapeutic progress in this space has historically been limited. Currently, only two targeted therapies—sotorasib (Lumakras; Amgen) and adagrasib (Krazati; Mirati Therapeutics)—have received FDA approval, both indicated for second-line treatment following chemotherapy.⁴

Despite these advances, clinical benefit remains modest, with disease-free survival rates around 30% and a median duration of response of approximately 5 to 6 months. Although both agents have demonstrated improvements compared with docetaxel, outcomes underscore the ongoing need for more durable and effective options.⁴

The field of KRAS inhibition is rapidly evolving, with multiple next-generation agents currently in clinical development. Ongoing studies are exploring monotherapy and combination approaches, as well as agents that target the GDP-bound (inactive) form of KRAS and emerging pan-KRAS inhibitors designed to address resistance and broader mutation coverage.⁴

Conclusion

The evolution of molecularly targeted therapies has transformed the treatment landscape of NSCLC, turning what was once a fatal disease into one defined by precision and personalization. As highlighted by Wolf, the continued integration of comprehensive molecular diagnostics remains essential to ensuring that each patient receives the most effective therapy for their unique tumor profile. According to Wolf:

“Continuous innovation demands not only better products, but also better data, smarter networks and genuine partnership with our patients to guide everyday decisions”

REFERENCES

1. Key Statistics for lung cancer. American Cancer Society. Updated January 16, 2025. Accessed October 18, 2025. https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html

2. Gerlach A. Zongertinib receives breakthrough therapy designation for patients with HER2 non-small cell lung cancer. Pharmacy Times. September 4, 2025. Accessed October 18, 2025. https://www.pharmacytimes.com/view/zongertinib-receives-breakthrough-therapy-designation-for-patients-with-her2-non-small-cell-lung-cancer

3. Eldridge L. Lung cancer survival rates by type, age, and stage. Very Well Health. Updated April 14, 2025. Accessed October 18, 2025. https://www.verywellhealth.com/lung-cancer-survival-rates-by-type-and-stage-2249401#:~:text=The%20survival%20rate%20for%20lung,also%20contribute%20to%20your%20survival.

4. Wolf J, Jänne P, Leighl N. Targeting oncogenes in NSCLC. Presented at: European Society for Medical Oncology 2025 Congress. October 17, 2025, to October 21, 2025. Berlin, Germany.

5. Gerlach A. Navigating EGFR mutations and ALK fusions in early-stage non-small cell lung cancer. Pharmacy Times. July 19, 2025. Accessed October 18, 2025. https://www.pharmacytimes.com/view/navigating-egfr-mutations-and-alk-fusions-in-early-stage-non-small-cell-lung-cancer

6. FDA approves osimertinib as adjuvant therapy for non-small cell lung cancer with EGFR mutations. FDA. December 18, 2024. Accessed October 18, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-osimertinib-adjuvant-therapy-non-small-cell-lung-cancer-egfr-mutations

7. AZD9291 versus placebo in patients with stage IB-IIIA non-small cell lung carcinoma, following complete tumour resection with or without adjuvant chemotherapy. (ADAURA). Clinicaltrials.gov. August 28, 2025. Accessed October 18, 2025. https://clinicaltrials.gov/study/NCT02511106

8. FDA approves osimertinib for locally advanced, unresectable (stage III) non-small cell lung cancer following chemoradiation therapy. FDA. September 25, 2024. Accessed October 18, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-osimertinib-locally-advanced-unresectable-stage-iii-non-small-cell-lung-cancer

9. A Global Study to Assess the Effects of Osimertinib Following Chemoradiation in Patients With Stage III Unresectable Non-small Cell Lung Cancer (LAURA) (LAURA). Clinicaltrials.gov. October 16, 2025. Accessed October 18, 2025. https://clinicaltrials.gov/study/NCT03521154

10. A study of osimertinib with or without chemotherapy as 1st line treatment in patients with mutated epidermal growth factor receptor non-small cell lung cancer (FLAURA2) (FLAURA2). Clinicaltrials.gov. October 10, 2025. Accessed October 18, 2025. https://clinicaltrials.gov/study/NCT04035486

11. A study of amivantamab and lazertinib combination therapy versus osimertinib in locally advanced or metastatic non-small cell lung cancer (MARIPOSA). Clinicaltrials.gov. September 15, 2025. Accessed October 18, 2025. https://clinicaltrials.gov/study/NCT04487080

12. A study of osimertinib with or without chemotherapy versus chemotherapy alone as neoadjuvant therapy for patients with eGFRm positive resectable non-small cell lung cancer (NeoADAURA). Clinicaltrials.gov. May 23, 2025. Accessed October 18, 2025. https://www.clinicaltrials.gov/study/NCT04351555

13. A study of lorlatinib versus crizotinib in first line treatment of patients with ALK-positive NSCLC. Clinicaltrials.gov. December 24, 2024. Accessed October 18, 2025. https://clinicaltrials.gov/study/NCT03052608

14. D’Angelo A, Sobhani N, Chapman R, et a;. Focus on ROS1-Positive Non-Small Cell Lung Cancer (NSCLC): Crizotinib, Resistance Mechanisms and the Newer Generation of Targeted Therapies. Cancers (Basel). November 6, 2020. doi: 10.3390/cancers12113293. PMID: 33172113

15. FDA grants accelerated approval to datopotamab deruxtecan-dlnk for EGFR-mutated non-small cell lung cancer. FDA. June 23, 2025. Accessed October 18, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-datopotamab-deruxtecan-dlnk-egfr-mutated-non-small-cell-lung-cancer

16. FDA grants accelerated approval to zongertinib for non-squamous NSCLC with HER2 TKD activating mutations. FDA. August 8, 2025. Accessed October 18, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zongertinib-non-squamous-nsclc-her2-tkd-activating-mutations

17. Beamion LUNG-1: a study to test different doses of zongertinib in people with different types of advanced cancer (solid tumours with changes in the HER2 Gene). Updated July 28, 2025. Accessed October 18, 2025. https://clinicaltrials.gov/study/NCT04886804#study-overview

18. Gerlach A. Zongertinib receives breakthrough therapy designation for patients with HER2 non-small cell lung cancer. Pharmacy Times. September 4, 2025. Accessed October 18, 2025. https://www.pharmacytimes.com/view/zongertinib-receives-breakthrough-therapy-designation-for-patients-with-her2-non-small-cell-lung-cancer

This article first appeared on GuruFocus.

Following the October 11 market correction, risk-off sentiment swept across global crypto markets. Yet, within days, the Trump family’s digital-asset ecosystem including the WLFI platform, the USD1 stablecoin, and American Bitcoin (ABTC) delivered substantial gains. Independent estimates suggest roughly $1.3 billion in new wealth creation, pushing the family’s total net worth to around $7.7 billion. Supporters hail the momentum as a sign of market recovery, while critics warn of regulatory capture and conflicts of interest. The convergence of policy and capital has become a defining feature of this new policy-driven market.

Policy-Capital Feedback Loop:

Since Donald Trump’s inauguration, regulatory posture has softened and pending litigation settlements have accelerated. Liquidity has flowed back into crypto markets, lifting correlated assets tied to the Trump ecosystem.

Two Primary Growth Engines:

• WLFI: Governance-token unlock and institutional accumulation.

• USD1: After the federal compliance framework (Genius Act) took effect, the reserve-based model began generating significant interest income and network expansion.

Industrial Backbone:American Bitcoin (ABTC) went public via merger and Nasdaq listing, seeing sharp intraday volatility and rapid valuation gains.

Core Controversy:The boundary between regulator and regulated remains blurred. The role of offshore capital introduces national-security and governance-integrity concerns.

• Jan 2025: SEC leadership reshuffle ? enforcement pivot.

• Mar Aug 2025: ABTC formed and completed merger with a listed entity.

• Jul 2025: Federal Stablecoin Framework (Genius Act) signed into law.

• Aug 2025: Alt5 Sigma announces $1.5 billion allocation to WLFI.

• Sept 1 2025: WLFI lists publicly ? peak valuation ? $7 billion.

• Sept 3 2025: ABTC debuts on Nasdaq ? intraday valuation ? $13.2 billion.

1. WLFI Governance Token: Market debut and institutional buying boosted capitalization and liquidity.

2. USD1 Stablecoin: Interest income from reserve assets and ecosystem integration magnified cashflow.

3. ABTC Equity Holdings: Public-market repricing increased book value.

Across multiple independent reports, the Trump family’s paper and realized gains for Q3 2025 are estimated around $1.3 billion, with aggregate net worth now near $7.7 billion, including unrealized holdings.

• Policy Reversal: Mid-term politics and regulatory realignment could drive valuation retracement.

• Governance & Ethics: Potential conflicts of interest and offshore funding influence demand greater audit transparency.

• Market Volatility: Post-October 11 secondary sell-offs suggest liquidity recovery remains incomplete.

This case illustrates how policy markets precede fundamentals.Investors should watch for early signals of capital rotation such as:

• Rising political donations ? policy commitments ? fast-track implementation ? market inflows. Asset selection should focus on sustainable cashflow, audited transparency, policy resilience, and liquidity management.

Amid heightened volatility, some investors have shifted from price speculation toward cashflow anchoring.NB HASH, a global digital-income platform established in 2019, offers a regulated and automated pathway for generating daily returns through transparent digital-asset contracts positioning itself as a potential cashflow buffer during high-volatility cycles.

Highlights:

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Consolidation therapy with tiragolumab plus atezolizumab (Tecentriq) failed to meet the primary end point of improving independent review facility (IRF)-assessed progression-free survival (PFS) vs standard durvalumab (Imfinzi) in patients with locally advanced, unresectable, stage III non–small cell lung cancer (NSCLC) that has not progressed after platinum-based concurrent chemoradiation (cCRT), according to findings from the phase 3 SKYSCRAPER-03 trial presented at the 2025 ESMO Congress.¹

At a median follow-up of 30.7 months, the median IRF-PFS in the overall population was 14.2 month (95% CI, 12.6-19.2) in patients receiving the combination vs 13.8 months (95% CI, 10.9-17.0) in patients treated with durvalumab (HR, 1.00; 95% CI, 0.84-1.19). The 24-month PFS event-free rates were 39.0% and 38.5%, respectively. The median overall survival (OS) was 45.6 months (95% CI, 37.1–not evaluable [NE]) vs 45.8 months (95% CI, 36.9-NE), respectively (HR, 0.98; 95% CI, 0.80-1.20). The 24-month OS event-free rates were 67.0% vs 66.3%, respectively.

The primary end point was also missed in PD-L1–positive patients (Tumor Cell [TC] score ≥1%) with a median IRF-PFS of 19.4 months vs 16.6 months in patients treated with the combination vs durvalumab, respectively (HR, 0.96; 95% CI, 0.75-1.23; P = .7586). The median OS in these patients was NE vs 54.8 months, respectively (HR, 0.99; 95% CI, 0.73-1.34). The 24-month PFS and OS event-free survival rates were 46.1% vs 42.9% and 72.2% vs 69.2%, respectively.

“SKYSCRAPER-03 did not meet its primary end point of IRF-PFS. There were no new or unexpected [safety] findings,” said first study author Rafal Dziadziuszko, MD, PhD, department of oncology and radiotherapy of the Medical University of Gdansk, Poland.

What Was the Safety Profile of the Combination and Monotherapy Arms in the SKYSCRAPER-03 trial?

“Tiragolumab plus atezolizumab demonstrated a tolerable safety profile, consistent with previous observations for the combination,” said Dziadziuszko.

Grade 3/4 treatment-related adverse events (TRAEs) occurred in 13.8% of patients in the combination arm, with serious TRAEs experienced by 11.5%. There were 2 patient deaths considered to be related to the combination treatment. In the durvalumab arm, grade 3/4 TRAEs and serious TRAEs each occurred in 10.7% of patients. There were 7 patient deaths considered to be related to durvalumab treatment.

What Was the Study Rationale and Design for the SKYSCRAPER-03 trial?

Regarding the rationale for the study, Dziadziuszko explained, “Consolidation durvalumab is the standard of care for patients with unresectable, stage III NSCLC that has not progressed following cCRT; however, disease recurrence [still] represents an unmet need.”

He added that the immune checkpoint target TIGIT has a role in cancer immune evasion and the study hypothesis was that tiragolumab, an anti-TIGIT monoclonal antibody, could potentially augment antitumor activity when used in combination with immunotherapies such atezolizumab.

The open-label phase 3 SKYSCRAPER-03 trial was launched to test this hypothesis in patients with newly diagnosed, unresectable, stage III NSCLC whose disease has not progressed following at least 2 cycles of definitive platinum-based cCRT. Patients had to have known PD-L1 status, and an ECOG performance status of 0 or 1. Patients with EGFR– or ALK-positive tumors were not eligible for enrollment.

At 1 to 42 days post cCRT, patients were randomized in a 1 to 1 ratio to combination therapy with tiragolumab (840 mg IV every 4 weeks) plus atezolizumab (1680 mg IV every 4 weeks) or single-agent durvalumab (10 mg/kg IV every 2 weeks or 1500 mg IV every 4 weeks). Patient could receive up to 13 cycles of treatment (28-day cycles).

The primary end point was PFS assessed by an independent review facility in patients with PD-L1–positive (Tumor Cell [TC] score ≥1%) as well as PD-L1 all-comers. Secondary end points included OS, duration of response, objective response rate, patient-reported outcomes, and safety.

What Were the Patient Characteristics in the SKYSCRAPER-03 trial?

Patient characteristics were well balanced between the 2 study arms. The median age was 64 years (range, 35-84) in the combination arm vs 65 years (range, 41-86) in the durvalumab arm. About half of patients in each arm were aged less than 65 years at 50.8% and 47.4%, respectively. About 80% of patients in each arm were male, about 60% were White, and about 35% were Asian. Patients’ ECOG performance status was mostly split evenly between 0 and 1, with a slightly higher number of patients in each arm at ECOG 1 status. About 75% of patients in each arm were former tobacco users and about 20% were current tobacco users.

About 50% of patients in each arm had a PD-L1 TC score of <1%, with about 25% of patients having a score of 1%-49%, and the remaining patients having a score of ≥50%. Tumor staging prior to definitive cCRT showed that 41.1% of patients receiving the combination had stage IIIA tumors vs 39.6% of patients in the single-agent arm. Rates of stage IIIB and stage IIIC tumors were 47.4% vs 44.4% and 11.4% vs 16.0%, respectively. About 60% of patients in each arm had squamous histology and about 40% had non-squamous histology. Best response to concurrent chemoradiotherapy in the combination vs durvalumab arms was complete response (0.5% in each arm), partial response (59.7% vs 61.4%), and stable disease (39.8% vs 38.1%).

In his concluding remarks, Dziadziuszko did not report any next steps for the combination of tiragolumab plus atezolizumab in this setting.

Disclosures

Dziadziuszko disclosed relationships with AstraZeneca, Boehringer Ingelheim, BMS, Pfizer, Takeda, Eli Lilly, BioNTech, Novartis, and Roche.

Reference

1. Dziadziuszko R, Ahn M-J, Bradley JD, et al. SKYSCRAPER-03: Phase III, open-label, randomised study of atezolizumab (atezo) + tiragolumab (tira) vs durvalumab (durva) in locally advanced, unresectable, stage III non-small cell lung cancer (NSCLC) after platinum-based concurrent chemoradiation (cCRT). Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA69.

(Bloomberg) — China’s economy probably grew at the slowest in a year during the third quarter despite a boom in exports, in a disconnect the Communist Party may move to rectify at a key meeting in the coming week.

Most Read from Bloomberg

As trade tensions escalate with the US, weakness in investment, industrial output and retail sales is undermining momentum from record sales abroad. Data due on Monday from China’s National Bureau of Statistics will show gross domestic product rose 4.7% in the quarter from a year earlier, according to the median estimate in a Bloomberg survey, down from 5.2% in the prior three months.

Retail sales are forecast to have expanded 3% in September and industrial output to have climbed by 5% — the weakest outcomes this year for both.

Meanwhile, fixed-asset investment is forecast to have slowed again in the first nine months, to be unchanged from a year earlier. It’s been plunging since May despite a massive expansion in government borrowing meant to support the spending power of local authorities. Public spending on infrastructure hasn’t been enough, though, to make up for a slump in housing investment and the slowdown in money going to manufacturing.

Foreign firms have also been pulling back on outlays, with inbound new foreign direct investment down almost 13% in the first eight months, putting China on track for three straight years of declines. One bright spot is foreign demand, with the goods trade balance so far this year hitting a record $875 billion, according to the latest figures.

The economic fragility sets the tone for the upcoming gathering of party officials at the so-called fourth plenum in Beijing. The huddle will provide clues on their priorities for 2026-2030, as governments and investors around the world call for a rebalancing of China’s economy toward domestic consumption.

What Bloomberg Economics Says:

“Beijing now faces deep structural headwinds — from fading growth drivers to a protracted property downturn and entrenched deflation — unlike the severe, yet temporary pandemic shocks during the last five-year planning stage. With the US ratcheting up trade and tech restrictions, the external environment has also turned sharply adverse. This time, the transition is no longer a distant goal — it’s imperative.”

—Chang Shu, chief Asia economist. For full analysis, click here

The IMF, which just kept its prediction for China’s 2025 growth at 4.8%, expects a slowdown next year to 4.2% — an outlook in line with the median forecasts of economists surveyed by Bloomberg. The fund warned that “China’s prospects remain weak,” saying “real estate investment continues to shrink while the economy teeters on the verge of a debt-deflation cycle.”

“Rebalancing toward household consumption — including through fiscal measures with a greater focus on social spending and the property sector — and scaling back industrial policies would reduce external surpluses and alleviate domestic deflationary pressures,” the IMF officials said in their global economic outlook.

Elsewhere, inflation data from Japan to the UK, purchasing manager indexes from major economies, and the first summary of a meeting by Swiss central bank officials will be among the highlights.

Click here for what happened in the past week, and below is our wrap of what’s coming up in the global economy.

US and Canada

After being delayed by the US government shutdown, the Bureau of Labor Statistics will release of the September consumer price index on Friday. The data, originally slated for Oct. 15, will give Federal Reserve officials a critical piece of information on inflation ahead of their policy meeting the following week.

Economists in a Bloomberg survey forecast the core CPI, which excludes food and fuel for a better snapshot of underlying inflation, to have climbed 0.3% for a third straight month as higher import duties continue to gradually filter through to consumers. The projected monthly gain will keep the annual core CPI at 3.1%.

While most official economic data releases have been delayed, BLS staff were called in despite the shutdown to prepare the September CPI report, which informs next year’s cost-of-living adjustments for Social Security recipients.

Although inflation is stuck above their goal, Fed officials are expected to announce their second rate cut of the year following a two-day meeting on Oct. 28-29 because of the fragile labor market.

Among private-sector economic data on the agenda, a National Association of Realtors report on Thursday will probably show contract closings on purchases of previously owned homes stayed tepid in September. An S&P Global PMI release on Friday is projected to illustrate modest growth in manufacturing and services activity.

Asia

Apart from the busy week in China, Japan reports national CPI figures on Friday expected to show that consumer inflation remained well above the Bank of Japan’s target in September, while purchasing manager indexes the same day may show manufacturing activity shrinking for a fourth straight month, even as services marked a full year of expansion.

India’s September PMI figures will likely show manufacturing activity remains robust. New Zealand reports quarterly inflation data, while Malaysia, Singapore and Hong Kong release September CPI.

Monthly trade data are due from New Zealand, Thailand and Japan, while South Korea will release 20-day trade statistics for October.

On the policy front, China is likely to hold its 1- and 5-year loan prime rates steady on Monday. Bank Indonesia will mull another cut to its benchmark rate on Wednesday as it weighs benign inflation against the weakening rupiah.

A day later, the Bank of Korea is expected to hold its base rate steady at 2.50% while possibly foreshadowing a cut in November as inflation stays subdued and economic growth cools. Uzbekistan sets rate policy on Thursday.

Europe, Middle East, Africa

The week’s highlight may be the initial reading of October purchasing manager indexes across western Europe.

These will reveal how manufacturing and services companies in Germany, France and the UK assessed the activity at the start of the fourth quarter, pointing to any momentum — or lack thereof — at a time when President Donald Trump’s tariffs are squeezing exports to the US.

In terms of hard data, Britain may draw the most attention. Public finance numbers on Tuesday will inform Chancellor Rachel Reeves as she prepares for a fraught budget in November.

Inflation the following day will be crucial both for Reeve’s plans and the Bank of England, which is inching toward further rate cuts while nervously monitoring still-strong price pressures. The data are likely to show acceleration to 4%, the fastest in 1 1/2 years.

In the euro zone, several European Central Bank speakers will deliver remarks before a pre-decision quiet period kicks in on Thursday. Among them will be Executive Board members Isabel Schnabel and Philip Lane on Monday, and President Christine Lagarde on Wednesday.

Meanwhile, France’s ongoing struggles to pass a budget are likely to continue after Prime Minister Sebastien Lecornu survived two no-confidence votes in the past week. Political strife could yet force the collapse of his government.

The situtation was exacerbated by Friday night’s unscheduled move by S&P Global Ratings to downgrade the country. The move means France has lost its double-A rating at two of the three major credit assessors in little more than a month, potentially forcing some funds with ultra-strict investment criteria to sell the country’s bonds.

An update at Moody’s Ratings is due at the end of the coming week, though the firm currently has a stable outlook on the country.

Belgium is also on the calendar for a possible review from S&P Global Ratings, whose view on its credit score is already skewed negative.

In Switzerland on Tuesday, September export numbers will offer a glimpse into the country’s trade position at the end of a quarter when it got slapped with the highest US import tariffs of any advanced economy. The government cited those levies in cutting its growth forecast for next year.

Thursday will be a watershed moment for the Swiss National Bank with the release of its first-ever summary of a rate meeting discussion, in an attempt to emulate the sort of transparency practiced by the Fed.

Turning south, data on Wednesday will likely show South African inflation ticked up to 3.4% in September from 3.3%. That may again persuade policymakers to hold rates steady for a second consecutive meeting next month as they defend the South African Reserve Bank’s stricter 3% goal for price growth, which they signaled in July is their preferred level.

A day later, the central bank will publish its semi-annual monetary policy review and Governor Lesetja Kganyago will offer more insights.

Some monetary decisions are scheduled around the region:

• On Tuesday, the National Bank of Hungary is set to keep its rate on hold at 6.5%, having rebuffed government calls for easing.

• Turkey’s central bank is likely to lower rates again on Thursday — by 100 basis points to 39.5%, according to a Bloomberg survey. Still, some in the poll expect a hold after price growth unexpectedly picked up in September to 33.3% year-on-year.

• The Bank of Russia will announce its latest rate decision on Friday, after cuts at the past three meetings brought the benchmark to 17%. Governor Elvira Nabiullina has warned that the widening federal budget deficit, driven by spending on the war in Ukraine, may limit room for further cuts.

Latin America

In a light week, Mexico may face a second straight month of negative GDP-proxy prints for August, due largely to more restricted public spending and Trump’s trade policies.

In similar vein, August data from Argentina may show activity extending a slump as President Javier Milei’s shock therapy weighs on the economy.

Also due from Argentina is Torcuato Di Tella University’s government confidence index, which is fresh off a tumble and may have taken another leg down amid a sell-off of the peso and local assets. Much is riding on how Milei fares in the Oct. 26 midterm elections.

Providing regional contrast material, Colombia’s August GDP-proxy report comes on the heels of July data that showed growth got off to a blistering start in the second half, in line with central bank forecasts.

Mid-month inflation reports from Brazil and Mexico are likely to show still-simmering price pressures.

Sticky and elevated core readings are likely to keep Brazil’s central bank on hold at 15% into 2026, though readings in Mexico are very unlikely to see Banxico pause its easing cycle after 10 straight rate cuts.

–With assistance from Brian Fowler, Laura Dhillon Kane, Vince Golle, Monique Vanek, Robert Jameson, Mark Evans, Tony Halpin, Paul Abelsky and Paul Wallace.

Most Read from Bloomberg Businessweek

©2025 Bloomberg L.P.

Artificial intelligence (AI) represents a major opportunity for businesses across industries to develop products faster and cheaper than ever before. The race to gain a data-driven edge on the competition is fueling massive investment across the entire tech supply chain from data centers to software.

Many of the key players enabling this new industrial revolution are already valued at over $1 trillion market caps. But as governments and businesses continue to invest in this technology, there are two AI enablers that are still valued under $500 billion that could be worth buying today. Here’s why growing competition in AI could propel these companies into the trillion-dollar club.

Palantir (NASDAQ: PLTR) started as a government contractor, providing AI-powered software for intelligence and counterterrorism efforts. But now its software is experiencing insatiable demand in the private sector. Companies are seeing significant cost savings, which means Palantir can benefit from companies scrambling to adopt AI solutions to remain competitive.

If one company in an industry uses Palantir to gain operating efficiencies, it creates a competitive advantage. This pushes more businesses to consider investing in Palantir’s platforms or risk falling behind. This can explain in part why Palantir’s U.S. commercial revenue has exploded this year, nearly doubling year over year in the second quarter.

Palantir closed its highest quarter yet of total contract-value bookings of $2.3 billion, representing a year-over-year increase of 140%. It is signing bigger deals while also seeing existing customers continue to spend more, leading to a healthy 128% net-dollar retention rate.

Palantir is effectively a tool that improves a company’s profits. Its software is expensive relative to alternative software vendors, but Palantir still expects accelerating growth next quarter. This signals it has a competitive edge. Palantir’s ontology-based system creates a digital twin of a company’s operations, helping managers make sense of unorganized data for better decision making.

Importantly, Palantir is converting revenue into very high margins that are driving robust growth in earnings and free cash flow. This is one reason why the stock has performed so well and may continue to outperform Wall Street’s expectations.

For what it’s worth, widely followed tech analyst Dan Ives at Wedbush Securities sees Palantir stock hitting a market cap of $1 trillion in the next three years. Keep in mind, the stock trades at an expensive valuation, so market sentiment will play a role in how the stock performs in the near term. Given the potential for volatility in the share price, investors should plan on holding it for at least 10 years. Long term, the savings and efficiencies Palantir brings to other companies could make it one of the most valuable companies in the world.

The companies providing the chips for AI continue to benefit from increasing competition among the leading model builders. OpenAI just announced a deal to deploy six gigawatts of chips, which amounts to hundreds of thousands, from Advanced Micro Devices (NASDAQ: AMD) over the next several years.

OpenAI’s ChatGPT is the most popular AI model with over 700 million weekly active users. But to meet growing demand, it has to expand its compute capacity to compete with rivals, including xAI’s Grok and Google Gemini, which also continue to invest in more infrastructure. This growing competition will benefit AMD.

OpenAI’s deal with AMD validates the capabilities of its upcoming pipeline of graphics processing units (GPUs). AMD’s data center business has not been growing as fast as Nvidia‘s, but it is expected to accelerate over the next year, and the deal with OpenAI is a catalyst.

While Nvidia’s GPUs have been widely used by data centers for powering large AI training loads, AMD’s chips have an advantage in handling small-to-medium-sized AI tasks. This is by design. AMD’s Instinct family of GPUs feature a high amount of memory bandwidth that makes them well suited for the AI inference market, which CEO Lisa Su believes is going to be much bigger than AI training.

OpenAI will deploy the first gigawatt of AMD Instinct MI450 GPUs in the second half of 2026. Analysts currently expect AMD’s revenue to grow 28% in 2025 before increasing by 26% in 2026, according to Yahoo! Finance. Earnings should grow even faster due to the high margins of data center GPUs.

The stock currently has a market cap of $350 billion. Assuming the stock continues to trade around the same price-to-earnings (P/E) multiple, AMD has a good chance to reach a $1 trillion market cap by 2030. Wall Street analysts expect earnings to grow at an annualized rate of 34%, which is enough to generate outstanding returns for investors.

Before you buy stock in Palantir Technologies, consider this:

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John Ballard has positions in Advanced Micro Devices, Nvidia, and Palantir Technologies. The Motley Fool has positions in and recommends Advanced Micro Devices, Alphabet, Nvidia, and Palantir Technologies. The Motley Fool has a disclosure policy.

Prediction: Global AI Competition Could Create Trillion-Dollar Winners was originally published by The Motley Fool

(Bloomberg) — China’s economy probably grew at the slowest in a year during the third quarter despite a boom in exports, in a disconnect the Communist Party may move to rectify at a key meeting in the coming week.

As trade tensions escalate with the US, weakness in investment, industrial output and retail sales is undermining momentum from record sales abroad. Data due on Monday from China’s National Bureau of Statistics will show gross domestic product rose 4.7% in the quarter from a year earlier, according to the median estimate in a Bloomberg survey, down from 5.2% in the prior three months.

Retail sales are forecast to have expanded 3% in September and industrial output to have climbed by 5% — the weakest outcomes this year for both.

Meanwhile, fixed-asset investment is forecast to have slowed again in the first nine months, to be unchanged from a year earlier. It’s been plunging since May despite a massive expansion in government borrowing meant to support the spending power of local authorities. Public spending on infrastructure hasn’t been enough, though, to make up for a slump in housing investment and the slowdown in money going to manufacturing.

Foreign firms have also been pulling back on outlays, with inbound new foreign direct investment down almost 13% in the first eight months, putting China on track for three straight years of declines. One bright spot is foreign demand, with the goods trade balance so far this year hitting a record $875 billion, according to the latest figures.

The economic fragility sets the tone for the upcoming gathering of party officials at the so-called fourth plenum in Beijing. The huddle will provide clues on their priorities for 2026-2030, as governments and investors around the world call for a rebalancing of China’s economy toward domestic consumption.

What Bloomberg Economics Says:

“Beijing now faces deep structural headwinds — from fading growth drivers to a protracted property downturn and entrenched deflation — unlike the severe, yet temporary pandemic shocks during the last five-year planning stage. With the US ratcheting up trade and tech restrictions, the external environment has also turned sharply adverse. This time, the transition is no longer a distant goal — it’s imperative.”

—Chang Shu, chief Asia economist. For full analysis, click here

The IMF, which just kept its prediction for China’s 2025 growth at 4.8%, expects a slowdown next year to 4.2% — an outlook in line with the median forecasts of economists surveyed by Bloomberg. The fund warned that “China’s prospects remain weak,” saying “real estate investment continues to shrink while the economy teeters on the verge of a debt-deflation cycle.”

“Rebalancing toward household consumption — including through fiscal measures with a greater focus on social spending and the property sector — and scaling back industrial policies would reduce external surpluses and alleviate domestic deflationary pressures,” the IMF officials said in their global economic outlook.

Elsewhere, inflation data from Japan to the UK, purchasing manager indexes from major economies, and the first summary of a meeting by Swiss central bank officials will be among the highlights.

Click here for what happened in the past week, and below is our wrap of what’s coming up in the global economy.

US and Canada

After being delayed by the US government shutdown, the Bureau of Labor Statistics will release of the September consumer price index on Friday. The data, originally slated for Oct. 15, will give Federal Reserve officials a critical piece of information on inflation ahead of their policy meeting the following week.

Economists in a Bloomberg survey forecast the core CPI, which excludes food and fuel for a better snapshot of underlying inflation, to have climbed 0.3% for a third straight month as higher import duties continue to gradually filter through to consumers. The projected monthly gain will keep the annual core CPI at 3.1%.

While most official economic data releases have been delayed, BLS staff were called in despite the shutdown to prepare the September CPI report, which informs next year’s cost-of-living adjustments for Social Security recipients.

Although inflation is stuck above their goal, Fed officials are expected to announce their second rate cut of the year following a two-day meeting on Oct. 28-29 because of the fragile labor market.

Among private-sector economic data on the agenda, a National Association of Realtors report on Thursday will probably show contract closings on purchases of previously owned homes stayed tepid in September. An S&P Global PMI release on Friday is projected to illustrate modest growth in manufacturing and services activity.

For more, read Bloomberg Economics’ full Week Ahead for the US Asia

Apart from the busy week in China, Japan reports national CPI figures on Friday expected to show that consumer inflation remained well above the Bank of Japan’s target in September, while purchasing manager indexes the same day may show manufacturing activity shrinking for a fourth straight month, even as services marked a full year of expansion.

India’s September PMI figures will likely show manufacturing activity remains robust. New Zealand reports quarterly inflation data, while Malaysia, Singapore and Hong Kong release September CPI.

Monthly trade data are due from New Zealand, Thailand and Japan, while South Korea will release 20-day trade statistics for October.

On the policy front, China is likely to hold its 1- and 5-year loan prime rates steady on Monday. Bank Indonesia will mull another cut to its benchmark rate on Wednesday as it weighs benign inflation against the weakening rupiah.

A day later, the Bank of Korea is expected to hold its base rate steady at 2.50% while possibly foreshadowing a cut in November as inflation stays subdued and economic growth cools. Uzbekistan sets rate policy on Thursday.

For more, read Bloomberg Economics’ full Week Ahead for Asia Europe, Middle East, Africa

The week’s highlight may be the initial reading of October purchasing manager indexes across western Europe.

These will reveal how manufacturing and services companies in Germany, France and the UK assessed the activity at the start of the fourth quarter, pointing to any momentum — or lack thereof — at a time when President Donald Trump’s tariffs are squeezing exports to the US.

In terms of hard data, Britain may draw the most attention. Public finance numbers on Tuesday will inform Chancellor Rachel Reeves as she prepares for a fraught budget in November.

Inflation the following day will be crucial both for Reeve’s plans and the Bank of England, which is inching toward further rate cuts while nervously monitoring still-strong price pressures. The data are likely to show acceleration to 4%, the fastest in 1 1/2 years.

In the euro zone, several European Central Bank speakers will deliver remarks before a pre-decision quiet period kicks in on Thursday. Among them will be Executive Board members Isabel Schnabel and Philip Lane on Monday, and President Christine Lagarde on Wednesday.

Meanwhile, France’s ongoing struggles to pass a budget are likely to continue after Prime Minister Sebastien Lecornu survived two no-confidence votes in the past week. Political strife could yet force the collapse of his government.

The situtation was exacerbated by Friday night’s unscheduled move by S&P Global Ratings to downgrade the country. The move means France has lost its double-A rating at two of the three major credit assessors in little more than a month, potentially forcing some funds with ultra-strict investment criteria to sell the country’s bonds.

An update at Moody’s Ratings is due at the end of the coming week, though the firm currently has a stable outlook on the country.

Belgium is also on the calendar for a possible review from S&P Global Ratings, whose view on its credit score is already skewed negative.

In Switzerland on Tuesday, September export numbers will offer a glimpse into the country’s trade position at the end of a quarter when it got slapped with the highest US import tariffs of any advanced economy. The government cited those levies in cutting its growth forecast for next year.

Thursday will be a watershed moment for the Swiss National Bank with the release of its first-ever summary of a rate meeting discussion, in an attempt to emulate the sort of transparency practiced by the Fed.

Turning south, data on Wednesday will likely show South African inflation ticked up to 3.4% in September from 3.3%. That may again persuade policymakers to hold rates steady for a second consecutive meeting next month as they defend the South African Reserve Bank’s stricter 3% goal for price growth, which they signaled in July is their preferred level.

A day later, the central bank will publish its semi-annual monetary policy review and Governor Lesetja Kganyago will offer more insights.

For more, read Bloomberg Economics’ full Week Ahead for EMEA Some monetary decisions are scheduled around the region:

On Tuesday, the National Bank of Hungary is set to keep its rate on hold at 6.5%, having rebuffed government calls for easing. Turkey’s central bank is likely to lower rates again on Thursday — by 100 basis points to 39.5%, according to a Bloomberg survey. Still, some in the poll expect a hold after price growth unexpectedly picked up in September to 33.3% year-on-year. The Bank of Russia will announce its latest rate decision on Friday, after cuts at the past three meetings brought the benchmark to 17%. Governor Elvira Nabiullina has warned that the widening federal budget deficit, driven by spending on the war in Ukraine, may limit room for further cuts. Latin America

In a light week, Mexico may face a second straight month of negative GDP-proxy prints for August, due largely to more restricted public spending and Trump’s trade policies.

In similar vein, August data from Argentina may show activity extending a slump as President Javier Milei’s shock therapy weighs on the economy.

Also due from Argentina is Torcuato Di Tella University’s government confidence index, which is fresh off a tumble and may have taken another leg down amid a sell-off of the peso and local assets. Much is riding on how Milei fares in the Oct. 26 midterm elections.

Providing regional contrast material, Colombia’s August GDP-proxy report comes on the heels of July data that showed growth got off to a blistering start in the second half, in line with central bank forecasts.

Mid-month inflation reports from Brazil and Mexico are likely to show still-simmering price pressures.

Sticky and elevated core readings are likely to keep Brazil’s central bank on hold at 15% into 2026, though readings in Mexico are very unlikely to see Banxico pause its easing cycle after 10 straight rate cuts.

For more, read Bloomberg Economics’ full Week Ahead for Latin America –With assistance from Brian Fowler, Laura Dhillon Kane, Vince Golle, Monique Vanek, Robert Jameson, Mark Evans, Tony Halpin, Paul Abelsky and Paul Wallace.

©2025 Bloomberg L.P.

Interim data from the phase 3 DESTINY-Breast05 trial (NCT04622319) shared at the 2025 European Society for Medical Oncology (ESMO) Congress showed improved invasive disease–free survival (IDFS) with fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) gin compared with ado-trastuzumab emtansine (T-DM1; Kadcyla) in patients with high-risk, HER2-positive primary breast cancer with residual invasive disease following neoadjuvant therapy.¹

Treatment with T-DXd (n = 818) led to a 53% reduction in the risk of invasive disease or death compared with T-DM1 (n = 817; HR, 0.47; 95% CI, 0.34–0.66; P < .0001). The 3-year IDFS rates were 92.4% (95% CI, 89.7%–94.4%) with T-DXd vs 83.7% (95% CI, 80.2%–86.7%) with T-DM1.

“Patients benefited [from T-DXd] irrespective of age cohorts, region of accrual, hormone receptor status, disease status at presentation, post-therapy pathologic nodal status, and dual or single HER2-targeted therapy, as well as irrespective of the sequence or usage of radiation therapy for that minority of patients who did not receive [radiation] treatment,” Charles E. Geyer Jr., MD, said in the presentation.

Geyer is a professor of medicine and chief of the Division of Malignant Hematology and Medical Oncology at the University of Pittsburgh Medical Center Hillman Cancer Center in Pennsylvania.

What Was the Rationale for DESTINY-Breast05?

Previously, the phase 3 KATHERINE trial (NCT01772472 ) showed that T-DM1 improved IDFS (HR, 0.50; 95% CI, 0.39-0.64; P < .0001) and overall survival (OS; HR, 0.66; 95% CI, 0.51-0.87; P = .0027) compared with trastuzumab in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant therapy.² However, patients with advanced locoregional disease or positive nodal status following neoadjuvant therapy had 3-year IDFS rates of 76% and 83%, respectively; the 7-year IDFS rates were 67% and 72%, respectively.¹ These data reinforce the unmet need for improved post-neoadjuvant treatment in this population, Geyer emphasized.

What Was the Study Design?

This global, multicenter, randomized, open-label trial enrolled patients with residual invasive disease in the breast and/or axillary lymph nodes after neoadjuvant chemotherapy with a HER2-directed therapy. Patients needed to present with high-risk disease prior to neoadjuvant therapy, defined as inoperable early breast cancer or operable early breast cancer with axillary node–positive disease after neoadjuvant therapy. Patients also needed to have centrally confirmed HER2-positive disease and an ECOG performance status of 0 or 1. Enrolled patients were stratified by extent of disease at presentation (inoperable vs operable), type of HER2-targeted neoadjuvant therapy received (single vs dual), hormone receptor status (positive vs negative), and post-neoadjuvant therapy pathologic nodal status (positive vs negative).

Patients were randomly assigned 1:1 to receive intravenous (IV) T-DXd at 5.4 mg/kg every 3 weeks for 14 cycles, or IV T-DM1 at 3.6 mg/kg every 3 weeks for 14 cycles. Treatment was followed by a 40-day safety follow-up period.

Notably, concomitant adjuvant endocrine therapy was allowed per local practice protocols. Additionally, radiotherapy, if administered, could be initiated concurrently with study therapy or completed prior to the initiation of study therapy per the investigator. An interstitial lung disease (ILD) monitoring program was required for patients who received radiotherapy.

IDFS served as the primary end point, with disease-free survival (DFS) as a key secondary end point. Other secondary end points included OS, distant recurrence–free interval (DRFI), brain metastasis–free interval (BMFI), and safety.

What Did the Patient Population Look Like?

In total, 1635 patients were randomly assigned to receive T-DXd (n = 818) or T-DM1 (n = 817). In the T-DXd arm, 806 patients received treatment. A total of 27.7% of patients in this arm discontinued treatment due to adverse effects (AEs; 17.9%), patient withdrawal (7.4%), disease recurrence (0.2%), physician decision (1.9%), and protocol deviation (0.2%). In total, 72.3% of patients in this arm completed study treatment, and the median study duration was 29.9 months (range, 0.3-53.4).

In the T-DM1 arm, 801 patients received treatment. A total of 23.7% of patients in this arm discontinued treatment due to AEs (12.7%), patient withdrawal (6.2%), disease recurrence (3.7%), physician decision (0.6%), protocol deviation (0.1%), and other reasons (0.1%). In total, 76.3% of patients in this arm completed study treatment, and the median study duration was 29.7 months (range, 0.1-54.4).

In the T-DXd arm, the median age was 50.3 years (range, 24–78), Asian patients were the most predominant race (48.8%), and most patients had HER2 3+ disease by immunohistochemistry (IHC) (82.6%), hormone receptor–positive disease (71.0%), inoperable disease (52.7%), positive nodal status (80.7%), received dual HER2-targeted therapy with trastuzumab plus pertuzumab (77.9%), prior anthracycline use (51.7%), and received prior adjuvant radiotherapy (93.4%). In the T-DM1 arm, the median age was 50.6 years (range, 21-83), Asian patients were the most predominant race (47.2%), and the highest proportions of patients had HER2 3+ disease by IHC (82.0%), hormone receptor–positive disease (71.4%), inoperable disease (51.9%), positive nodal status (80.5%), received dual HER2-targeted therapy with trastuzumab plus pertuzumab (78.5%), prior anthracycline use (48.8%), and received prior adjuvant radiotherapy (92.9%).

What Additional Efficacy Outcomes Were Observed?

Overall, investigators observed lower rates of distant and local recurrences, including central nervous system (CNS) recurrences, with T-DXd vs T-DM1. The numbers of patients with recurrences in these respective arms were as follows:

• Distant recurrence: n = 42 (non-CNS, n = 25; CNS, n = 17); n = 77 (non-CNS, n = 52; CNS, n = 25)
• Local invasive recurrence: n = 1; n = 5
• Regional recurrence: n = 1; n = 6
• Contralateral invasive disease: n = 0; n = 6
• Death without prior reported event: n = 7; n = 8

A DFS benefit was observed with T-DXd vs T-DM1 (HR, 0.47; 95% CI, 0.34–0.66; P < .0001). The 3-year DFS rates were 92.3% (95% CI, 89.5%–94.3%) with T-DXd vs 83.5% (95% CI, 79.9%–86.4%) with T-DM1.

DRFI, BMFI, and OS benefits were also seen with T-DXd vs T-DM1. The respective 3-year DRFI rates were 93.9% (95% CI, 91.4%–95.7%) and 86.1% (95% CI, 82.5%–89.1%); the HR was 0.49 (95% CI, 0.34–0.71) favoring the T-DXd arm. The respective 3-year BMFI rates were 97.6% (95% CI, 96.2%–98.5%) and 95.1% (95% CI, 93.6%–97.2%); the HR was 0.64 (95% CI, 0.35–1.17) favoring the T-DXd arm. The respective 3-year OS rates were 97.4% (95% CI, 95.8%–98.4%) and 95.7% (95% CI, 93.5%–97.2%); the HR was 0.61 (95% CI, 0.34–1.10) favoring the T-DXd arm.

Regarding on-study treatment exposure, in the T-DXd arm, the median study treatment duration was 9.8 months, and 72.3% of patients completed the planned 14 cycles of therapy. In the T-DM1 arm, the median study treatment duration was 9.7 months, and 76.3% of patients completed the planned 14 cycles of therapy. Notably, patients who discontinued the study before receiving 14 cycles of study treatment were permitted to receive an additional HER2-targeted therapy per standard of care (SOC) guidelines to complete 14 total cycles of HER2-targeted adjuvant therapy.

What Was the Safety Profile?

In the T-DXd arm, any-grade treatment-emergent AEs (TEAEs) were reported in 99.5% of patients, and 50.6% of patients experienced grade 3 or higher TEAEs. Serious TEAEs (17.4%) and those associated with drug discontinuation (17.9%; drug-related ILD/pneumonitis, 10.8%), drug interruptions (49.6%), dose reductions (26.4%), and deaths (0.4%; ILD/pneumonitis, n = 2; respiratory tract infection adjudicated as not ILD, n = 1) also occurred.

In the T-DM1 arm, any-grade TEAEs were reported in 98.4% of patients, and 51.9% of patients experienced grade 3 or higher TEAEs. Serious TEAEs (13.6%) and those associated with drug discontinuation (12.9%; drug-related ILD/pneumonitis, 2.5%), drug interruptions (41.1%), dose reductions (26.6%), and deaths (0.6%; leiomyosarcoma of the uterus, aneurysm, non-neutropenic sepsis, ovarian cancer, and traumatic pneumothorax, n = 1 each) also occurred.

The most commonly reported TEAEs in the T-DXd and T-DM1 arms, respectively, were nausea (71.3%; 29.3%), constipation (32.0%; 16.2%), decreased neutrophil counts (31.6%; 14.4%), vomiting (31.0%; 9.0%), decreased white blood cell counts (29.7%; 13.0%), fatigue (29.5%; 20.2%), radiation pneumonitis (28.8%; 27.0%), anemia (28.3%; 17.0%), increased aspartate aminotransferase levels (25.6%; 50.2%), increased alanine aminotransferase levels (23.7%; 45.3%), diarrhea (23.2%; 8.6%), decreased platelet counts (21.2%; 49.8%), decreased appetite (20.0%; 10.0%), headache (15.8%; 20.7%), and arthralgia (10.3%; 20.5%).

The rates of adjudicated drug-related ILD in the T-DXd and T-DM1 arms were as follows:

• Any-grade: 9.6% vs 1.6%
• Grade 1: 2.0% vs 1.0%
• Grade 2: 6.5% vs 0.6%
• Grade 3: 0.9% vs 0%
• Grade 4: 0% vs 0%
• Grade 5: 0.2% vs 0%

No differences in adjudicated drug-related ILD instances were observed based on adjuvant radiotherapy timing (sequential or concurrent). Investigators observed similar distributions of any-grade adjudicated drug-related ILD events with sequential (T-DXd arm, 10.7%; T-DM1 arm, 2.6%) and concurrent (9.6%; 1.0%) radiotherapy.

The rates of left ventricular dysfunction in the T-DXd and T-DM1 arms were as follows:

• Any-grade: 2.9% vs 1.7%
• Grade 1: 0.1% vs 0%
• Grade 2: 2.5% vs 1.4%
• Grade 3: 0.2% vs 0.4%
• Grade 4: 0% vs 0%
• Grade 5: 0% vs 0%

“Adjuvant T-DXd demonstrated superior efficacy with manageable safety in patients with high-risk, HER2-positive early breast cancer and residual invasive disease after neoadjuvant therapy, which represents a potential new SOC in this post-neoadjuvant setting,” Geyer concluded.

DISCLOSURES: Geyer reported receiving grants from or having contracts with Daiichi Sankyo, AstraZeneca, Roche/Genentech, and Exact Sciences; receiving meeting and/or travel support from Exact Sciences; receiving honoraria or travel expenses from Exact Sciences and Merck; and receiving support for the current presentation from Daiichi Sankyo and AstraZeneca.

REFERENCES:

1. Geyer CE, Park YH, Shao Z, et al. Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (pts) with high-risk human epidermal growth factor receptor 2–positive (HER2+) primary breast cancer (BC) with residual invasive disease after neoadjuvant therapy (tx): interim analysis of DESTINY-Breast05. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA1.

2. Kadcyla. Prescribing information. Genentech; revised May 2025. Accessed October 18, 2025. https://www.gene.com/download/pdf/kadcyla_prescribing.pdf