Category: 3. Business

Findings from a real-world, prospective, non-interventional cohort study conducted in Portugal showed that fruquintinib (Fruzaqla) had a manageable safety profile and produced an efficacy trend in patients with refractory metastatic colorectal cancer (mCRC).¹

Data presented in a poster at the 2025 ESMO Gastrointestinal Cancers Congress demonstrated that evaluable patients treated with fruquintinib (n = 23) experienced a median overall survival (OS) of 4.0 months (95% CI, 0.47-7.53) and a median progression-free survival (PFS) of 3.0 months (95% CI, 0.96-5.04).

In contrast, data from the phase 3 FRESCO-2 trial (NCT04322539) showed that patients with refractory mCRC treated with fruquintinib (n = 461) experienced a median OS of 7.4 months (95% CI, 6.7-8.2) compared with 4.8 months (95% CI, 4.0-5.8) for those given placebo (HR, 0.66; 95% CI, 0.55-0.80; P < .0001).² The median PFS was 3.7 months vs 1.8 months, respectively (HR, 0.32; 95% CI 0.27-0.39; P < .001).³

Lead study author, Dr Filipa R. Verdasca, and colleagues noted in the poster that the shorter OS and comparable PFS data between the real-world cohort and those given fruquintinib in FRESCO-2 could reflect broader comorbidities of a real-world population and differences in clinical practice. Verdasca is a member of the Department of Medical Oncology at Unidada Local de Saúde de São José in Lisbon, Portugal.

“To our knowledge, this is one of the first non-Asian, real-world datasets and one of the first analyzing sequencing results from trifluridine/tipiracil [TAS-102; Lonsurf] and bevacizumab [Avastin] followed by fruquintinib,” Verdasca and colleagues wrote in the poster. “Despite the small sample size and very short follow-up, we observed a manageable safety profile and an efficacy trend, despite modest outcomes, picturing a highly refractory disease setting and a possible role of previous treatments on VEGFR targeting.”

In November 2023, the FDA approved fruquintinib for the treatment of adult patients with mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy.⁴

In June 2024, the European Commission approved the agent for adult patients with mCRC who have been previously treated with available standard therapies, including fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, anti-VEGF agents, and anti-EGFR agents, and who have progressed on or are intolerant to treatment with either TAS-102 or regorafenib (Stivarga).⁵

Both of these approvals were supported by data from FRESCO-2.

Diving into the Real-World Cohort Study

To evaluate real-world outcomes for fruquintinib in a European population, investigators of the multicenter, prospective, non-interventional cohort study enrolled patients with mCRC treated with fruquintinib between January 2024 and March 2025 at 1 of 5 Portuguese centers.¹

Medical records were used to pull clinical and demographic data, and the Kaplan-Meier method was used to calculate time-to-event outcomes.

The median age of the real-world population was 61 years (range, 55-68). The majority of patients were male (70%), had left-sided tumors (57%), and underwent primary tumor resection (87%). Patients had an ECOG performance status of 0 (30%), 1 (57%), or 2 (13%). Forty-three percent of patients had RAS, BRAF, and HER2 wild-type disease, and 48% harbored NRAS or KRAS mutations. BRAF mutations and HER2 mutations were reported in 1 patient each (4%). Notably, no patients had mismatch repair–deficient disease.

At baseline, patients had 1 metastatic site (35%), 2 metastases (13%), 3 metastases (30%), or at least 4 metastases (22%). Metastatic sites included liver (57%), lung (61%), lymph node (48%), peritoneal (26%), bone (17%), and central nervous system (22%). One patient (4%) received 2 lines of therapy prior to fruquintinib; the remainder of the population received 3 prior lines of therapy (61%), or at least 4 prior lines (35%).

Real-World Safety Findings

Any-grade treatment-related adverse effects (TRAEs) were reported in 73.9% of patients (n including 17.4% who experienced grade 3/4 TRAEs. In the safety evaluable population (n = 17), the most common grade 1/2 TRAEs included fatigue (n = 11), hypertension (n = 6), anemia (n = 4), diarrhea (n = 4), nausea/vomiting (n = 2), hemorrhage (n = 2), and mucositis (n = 1). Grade 3/4 TRAEs comprised hypertension (n = 3), mucositis (n = 1), and fatigue (n = 1).

Toxicity or intercurrent events led to treatment discontinuation in 39% of patients, and 30% of patients required dose reductions. The minimum dose received across the full population (n = 23) was 3 mg/m² (13%), 4 mg/mg² (26%), or 5 mg/mg² (61%).

Study authors noted that the rate of grade 3 or higher AEs occurred in 63% of patients treated with fruquintinib during FRESCO-2; however, the rates of treatment discontinuations (real-world, 39%; FRESCO-2, 20%) and dose reductions (30%; 24%) were higher in the cohort study, suggesting that greater clinical frailty and tolerability challenges in clinical practice may have influenced the increased rates.

“We intend to broaden our accrual and increase follow-up time to evaluate safety and more mature outcomes,” study authors concluded.

References

1. Verdasca FR, Martins AP, Fernandes ACB, et al. Real-world data from fruquintinib in later line metastatic colorectal cancer. Presented at: 2025 ESMO Gastrointestinal Cancers Congress; July 2-5, 2025; Barcelona, Spain. Abstract 66P.
2. Dasari A, Lonardi S, Garcia-Carbonero R, et al. Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, phase 3 study. Lancet. 2023;402(10395):41-53. doi:10.1016/S0140-6736(23)00772-9
3. HUTCHMED highlights phase III FRESCO-2 MRCT data summary of fruquintinib in refractory metastatic colorectal cancer from the upcoming ESMO 2022 presentation. News release. HUTCHMED. September 8, 2022. Accessed July 2, 2025. https://www.hutch-med.com/fruquintinib-fresco-2-data-summary-esmo-2022/
4. FDA approves fruquintinib in refractory metastatic colorectal cancer. FDA. November 8, 2023. Accessed July 2, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-fruquintinib-refractory-metastatic-colorectal-cancer
5. HUTCHMED announces European Commission approval for Fruzaqla (fruquintinib) received by Takeda. News release. HUTCHMED. June 21, 2024. Accessed July 2, 2025. https://www.hutch-med.com/european-commission-approval-for-fruzaqla-fruquintinib/

Objective response rate (ORR), median duration of response (DOR), median progression-free survival (PFS), and median overall survival (OS) were numerically higher or extended with the combination of encorafenib (Braftovi), cetuximab (Erbitux; EC), and mFOLFOX6 (modified fluorouracil plus leucovorin and oxaliplatin), irrespective of control arm regimen, in patients with BRAF V600E–mutant metastatic colorectal cancer (mCRC), according to data from a subgroup analysis of the phase 3 BREAKWATER study (NCT04607421).¹

Findings presented during the 2025 ESMO Gastrointestinal Cancer Congress showed the confirmed ORR by blinded independent central review (BICR) was 65.7% (95% CI, 59.4%-71.4%) with EC plus mFOLFOX6 (n = 236) vs 55.9% (95% CI, 43.3%-67.8%) with FOLFOXIRI (fluorouracil plus leucovorin, oxaliplatin, and irinotecan) plus bevacizumab (Avastin; n = 59), 50.0% (95% CI, 21.5%-78.5%) with FOLFOXIRI (n = 8), 38.1% (95% CI, 29.1%-48.1%) with mFOLFOX6 plus bevacizumab (n = 97), 22.2% (95% CI, 9.0%-45.2%) with mFOLFOX6 (n = 18), 29.3% (95% CI, 17.6%-44.5%) with CAPOX (capecitabine plus oxaliplatin) plus bevacizumab (n = 41), and 16.7% (95% CI, 3.0%-56.4%) with CAPOX (n = 6).

The median DORs were 13.9 months (95% CI, 10.9-18.5) with EC plus mFOLFOX6, 9.8 months (95% CI, 7.9-not evaluable [NE]) with FOLFOXIRI plus bevacizumab, 10.8 months (95% CI, 6.0-NE) with mFOLFOX6 plus bevacizumab, 9.7 months (95% CI, NE-NE) with mFOLFOX6, and 11.1 months (95% CI, 2.9-13.4) with CAPOX plus bevacizumab. In the EC plus mFOLFOX6 arm, 71.0% of patients experienced a DOR of at least 6 months, and 34.8% experienced a DOR of at least 12 months.

The median PFS with EC plus mFOLFOX6, FOLFOXIRI plus bevacizumab, mFOLFOX6 plus bevacizumab, mFOLFOX6, and CAPOX plus bevacizumab was 12.8 months (95% CI, 11.2-15.9), 10.1 months (95% CI, 8.3-13.7), 6.8 months (95% CI, 5.7-8.5), 4.3 months (95% CI, 2.7-11.0), and 5.9 months (95% CI, 4.5-9.9), respectively. The median OS in the respective groups was 30.3 months (95% CI, 2.17-NE), 17.4 months (95% CI, 14.3-23.4), 14.7 months (95% CI, 12.7-17.6), 11.6 months (95% CI, 7.5-19.6), and 14.5 months (95% CI, 11.2-22.2).

“These results are consistent with previous analyses of chemotherapy with or without bevacizumab in the first-line for the treatment of BRAF V600E mCRC,” Takayuki Yoshino, MD, PhD, of National Cancer Center Hospital East in Kashiwa, Japan, and coauthors, wrote in a poster of the data, which “[support] EC plus mFOLFOX6 as a practice-changing, new standard of care for BRAF V600E–mutant mCRC, including the first-line setting.”

Breaking Down BREAKWATER

The open-label, multicenter, phase 3 study enrolled patients with BRAF V600E–mutant mCRC who were at least 16 years of age—or at least 18 years of age based on country—with measurable disease by RECIST 1.1 criteria, an ECOG performance status of 0 or 1, and acceptable bone marrow, hepatic, and renal function. Patients could not have previously received systemic treatment for metastatic disease. Those with prior exposure to BRAF or EGFR inhibitors, symptomatic brain metastases, microsatellite instability–high/mismatch repair–deficient tumors, or RAS-mutated disease were excluded.

Patients (n = 637) were randomly assigned 1:1:1 to EC (n = 158), EC plus mFOLFOX6 (n = 236), or the control arm (n = 243) of mFOLFOX6/FOLFOXIRI/CAPOX with or without bevacizumab. Notably, the trial protocol was subsequently amended to limit randomization to the EC plus mFOLFOX6 arm and the control arm.²

Patients were stratified by region (US or Canada vs Europe vs rest of world) and ECOG performance status (0 vs 1).¹ The dual primary end points were PFS by BICR and ORR by BICR, and a key secondary end point was OS.

Both of the primary end points were met. The ORR—based on the first 110 patients enrolled to both groups—was 61% (95% CI, 52%-70%) in patients given EC plus mFOLFOX6 compared with 40% (95% CI, 31%-49%) for patients treated with chemotherapy with or without bevacizumab (Avastin; P = .0008).² The data supported the FDA’s decision to grant accelerated approval to EC plus mFOLFOX6 for use in patients with mCRC harboring a BRAF V600E mutation, as detected by an FDA-approved test, in December 2024. The median PFS with EC plus mFOLFOX6 was 12.8 months vs 7.1 months with standard care (HR, 0.53; 95% CI, 0.41-0.68; P < .001).³ In an interim analysis, OS was significantly longer with EC and mFOLFOX6 vs standard care, at a median of 30.3 months vs 15.1 months (HR, 0.49; 95% CI, 0.38-0.63; P < .001).

Examining the Current Subgroup Analysis

Of the total patients randomly assigned to the control arm (n = 243), 24.3% received FOLFOXIRI plus bevacizumab, 3.3% received FOLFOXIRI, 39.9% received mFOLFOX6 plus bevacizumab, 7.4% received mFOLFOX6, 16.9% received CAPOX plus bevacizumab, 2.5% received CAPOX, and 5.8% were not treated.

“Patients who received FOLFOXIRI plus bevacizumab were younger, and more patients were male, had ECOG performance status of 0, had 3 or more organs involved at baseline, and had left-sided tumors vs patients in the EC plus mFOLFOX6 and patients who received the other control regimens,” the study authors wrote.

The median follow-up for PFS in the EC plus mFOLFOX6 arm was 16.8 months (95% CI, 15.1-18.4) vs 9.8 months (95% CI, 8.5-13.0) in the control arm. The median follow-up for PFS in the respective arms was 21.8 months (95% CI, 20.4-23.4) and 22.2 months (95% CI, 18.9-23.5).

“The EC plus mFOLFOX6 arm had fewer patients discontinue study treatment compared with all control regimens,” the study authors wrote. The percentages of patients who discontinued study treatment in the EC plus mFOLFOX6, FOLFOXIRI plus bevacizumab, FOLFOXIRI, mFOLFOX6 plus bevacizumab, mFOLFOX6, CAPOX plus bevacizumab, and CAPOX were 71.6%, 86.4%, 87.5%, 94.8%, 100%, 95.1%, and 100%, respectively; the respective percentages of patients who received any subsequent systemic anticancer treatment were 45.8%, 59.3%, 75.0%, 58.8%, 55.6%, 63.4%, and 50.0%.

In the EC plus mFOLFOX6 arm, subsequent therapies included a BRAF inhibitor with or without combination (8.1%), CAPIRI with or without combination (4.7%), CAPOX with or without combination (0.8%), FOLFIRI with or without combination (24.2%), FOLFOX with or without combination (4.2%), FOLFOXIRI with or without combination (1.3%), fruquintinib (Fruzaqla; 0.4%), immunotherapy (0.4%), other (3.4%), regorafenib (Stivarga; 1.3%), single-agent chemotherapy with or without combination (7.2%), and trifluridine/tipiracil (Lonsurf) with or without VEGF inhibition (4.2%).

“Safety profiles were consistent with that known for each agent,” the study authors concluded.

Disclosures: Yoshino reported honoraria from Bayer Yakuhin, Chugai Pharma, Merck KGaA, MSD, Ono Pharmaceutical, Sumitomo Corp, and Takeda. Research funding was provided by Amgen, Boehringer Ingelheim, Chugai Pharma, Daiichi Sankyo Co Ltd, Eisai, FALCO Biosystems, Genomedia, Molecular Health, MSD, Nippin Boehringer Ingelheim, Ono Pharmaceutical, Pfizer, Roche Diagnostics, Sanofi, Sumitomo Dainippon, Sysmex, and Taiho Pharmaceutical.

References

1. Yoshino T, Kopetz S, Van Cutsem E, et al. BREAKWATER: Post-hoc subgroup analyses by chemotherapy ± bevacizumab regimens vs encorafenib plus cetuximab + mFOLFOX6. Presented at: 2025 ESMO Gastrointestinal Cancers Congress; July 2-5, 2025; Barcelona, Spain. Abstract 36P.
2. FDA grants accelerated approval to encorafenib with cetuximab and mFOLFOX6 for metastatic colorectal cancer with a BRAF V600E mutation. FDA. December 20, 2024. Accessed July 4, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-encorafenib-cetuximab-and-mfolfox6-metastatic-colorectal-cancer-braf
3. Elez E, Yoshino T, Shen L, et al. Encorafenib, cetuximab, and mFOLFOX6 in BRAF-mutated colorectal cancer. N Engl J Med. 2025;392(24):2425-2437. doi:10.1056/NEJMoa2501912

Jeff Bezos and Lauren Sanchez know how to leave a mark with everything they do.

The couple made headlines with a lavish $50 million wedding in Venice, Italy attended by a long list of celebrities and media personalities including Leonardo Dicaprio, Orlando Bloom, Sydney Sweeney, Kim Kardashian, Oprah Winfrey, Tom Brady and many more.

Now the newly-wed couple is off to spend their honeymoon at a location that has immense value for the TV fans.

As reported by Independent, the pair is at San Domenico Palace, a Four Seasons hotel in Taormina, Sicily.

The venue is internationally recognized for its role as the ‘setting’ for HBO series The White Lotus season two.

The 61-year-old and the 55-year-old reached the Nicelli airport from Venice to take a helicopter ride back to the Amazon founder’s $500 million superyacht Koru.

The yacht is currently anchored in Taormina while the two are enjoying some quality time together.

For the unversed, while the wedding has drawn backlash from some people including Charlize Theron and Rosie O’Donnell, the bride had prepared hard for the wedding.

The licensed pilot had brought some lifestyle changes including dietary to lose a few pounds before walking down the aisle.

Additionally, she also got a piercing on the nail of her ring finger to take her glam look up a notch.

The nail artist Iram Shelton pierced a diamond-encrusted ‘B’ charm into the long nail.

Findings from a subgroup analysis of the phase 3 CheckMate 9DW trial (NCT04039607) demonstrated that the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) provided overall survival (OS) and overall response rate (ORR) benefits compared with lenvatinib (Lenvima) or sorafenib (Nexavar) in Chinese patients with unresectable or advanced hepatocellular carcinoma (HCC).1

Data presented at the 2025 ESMO Gastrointestinal Cancers Congress showed that at a median follow-up of 31.3 months (range, 15.4-46.5), Chinese patients treated with nivolumab plus ipilimumab (n = 98) achieved a median overall survival (OS) of 23.5 months (95% CI, 18.0-37.8) compared with 20.1 months (95% CI, 15.3-24.0) in those given lenvatinib or sorafenib (n = 110; HR, 0.82; 95% CI, 0.57-1.18). The 24-month OS rates were 48% and 39%, respectively.

In the Chinese subgroup, nivolumab plus ipilimumab elicited an ORR of 37% (95% CI, 27%-47%) compared with 14% (95% CI, 8%-22%) for lenvatinib or sorafenib (difference, 23.1%; 95% CI, 11.4%-34.3%). The rates of complete and partial response were 7% and 30%, respectively, in the experimental arm. These respective rates were 2% and 12% in the lenvatinib or sorafenib arm.

“The results further support nivolumab plus ipilimumab as a potential new first-line standard-of-care therapy for patients with unresectable HCC in China, a region with the highest HCC incidence and overall mortality rate from HCC globally,” lead study author Shukui Qin, MD, of Nanjing Tianyinshan Hospital of China Pharmaceutical University, and colleagues wrote in a poster presentation of the data.

In April 2025, the FDA approved nivolumab in combination with ipilimumab for the first-line treatment of adult patients with unresectable or metastatic HCC, based on data from CheckMate 9DW.²

CheckMate 9DW and Subgroup Analysis Overview

The randomized, open-label study enrolled patients with unresectable HCC who were naive to systemic therapy in the unresectable/advanced setting.1 Patients needed to have at least 1 measurable lesion per RECIST 1.1 criteria, a Child-Pugh score of 5 or 6, and ECOG performance status of 0 or 1, and no main portal vein invasion.

Patients were randomly assigned 1:1 to receive nivolumab at 1 mg/kg plus ipilimumab at 3 mg/kg once every 3 weeks for up to 4 cycles, followed by nivolumab alone at 480 mg once every 4 weeks (n = 335); or single-agent treatment with investigator’s choice of lenvatinib at 8 mg or 12 mg per day, or sorafenib at 400 mg twice per day. Treatment continued until disease progression, unacceptable toxicity, or consent withdrawal. Treatment in the experimental arm only lasted for a maximum of 2 years.

Stratification factors included etiology (hepatitis B [HBV] vs hepatitis C vs uninfected); macrovascular invasion (MVI) or extrahepatic spread (EHS; yes vs no); and alpha-fetoprotein level (<400 ng/mL vs ≥400 ng/mL).

OS served as the trial’s primary end point. Blinded independent central review (BICR)–assessed ORR and duration of response (DOR), along with time to symptom progression, were secondary end points. BICR-assessed progression-free survival (PFS) and safety were exploratory end points.

The subgroup analysis included 208 Chinese patients from mainland China (n = 29), Hong Kong (n = 67), Taiwan (n = 48), and an additional group from mainland China (n = 64).

Within the Chinese subgroup, the median age was 63.5 years (range, 37-84) in the nivolumab/ipilimumab arm vs 62 years (range, 26-81) in the control arm. The majority of patients were male (experimental arm, 80%; control arm, 81%), had an HVB etiology (79%; 70%), had a Child-Pugh score of 5 (76%; 79%), and had Barcelona Clinic Liver Cancer stage C disease (78%; 74%). An ECOG performance status of 1 was reported in 35% of patients and 13% of patients in the respective arms.

In the nivolumab/ipilimumab arm at baseline, 30% of patients had MVI, 52% had EHS, and 66% had both. These respective rates were 31%, 55%, and 72% in the control arm. Forty-two percent of patients in the experimental arm had an AFP level of at least 400 ng/mL compared with 39% of patients in the lenvatinib/sorafenib arm. The rates of prior local therapy were 43% and 58%, respectively.

Additional Subgroup Efficacy Data

The median DOR was not reached (95%% CI, 23.4-not evaluable [NE]) in the nivolumab/ipilimumab arm vs 8.4 months (95% CI, 6.4-NE) in the lenvatinib or sorafenib arm. The median time to response was 2.1 months (95% CI, 1.8-9.1) and 5.5 months (95% CI, 1.9-13.9), respectively.

Among evaluable patients, the median tumor reduction from baseline was –47.1% (interquartile range [IQR], –70.5% to –4.8%) in the nivolumab/ipilimumab arm (n = 77) vs –13.8% (IQR, –28.2 to 1.2) in the control arm. Any reduction was reported in 75% of patients in the experimental arm vs 72% of patients in the control group. In the nivolumab/ipilimumab arm, tumor reductions of more than 50% and more than 75% occurred in 45% and 21% of patients, respectively. These respective rates were 5% and 1% in the control arm.

Further analyses showed that the ORR benefit with nivolumab/ipilimumab was consistent across subgroups within the Chinese population.

Any subsequent therapy was administered to 47% of Chinese patients in the nivolumab/ipilimumab arm vs 55% of patients in the lenvatinib or sorafenib group. These included radiotherapy (experimental arm, 6%; control arm, 5%), surgery (4%; 3%), locoregional therapy (14%; 12%), and systemic therapy (41%; 52%). Types of subsequent systemic therapy included anti–PD-(L)1 therapy (5%; 15%), anti–PD-(L)1 plus anti–CTLA-4 therapy (0%; 3%), anti–PD-(L)1 plus anti-VEGF therapy (12%; 19%); platinum-based chemotherapy (1%; 0%), and anti-VEGF therapy (30%; 15%).

The median time to second progression (PFS2) was 22.0 months (95% CI, 15.7-34.0) in the experimental arm vs 15.5 months (95% CI, 13.1-18.6) in the control arm (HR, 0.76; 95% CI, 0.54-1.09).

QOL and Safety Findings

Numerical improvements in health-related quality of life were reported with nivolumab/ipilimumab over the course of the study, with the exception of week 25. In the experimental arm, mean changes from baseline in Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) surpassed the minimal important difference (MID) of 8 points between weeks 53 and 89; however, in the control arm, FACT-Hep score worsened at several time points, and the MID was exceeded at week 61.

Regarding safety, any-grade treatment-related adverse effects (TRAEs) occurred in 90% of patients in the nivolumab/ipilimumab arm vs 95% of patients treated with lenvatinib or sorafenib. The rates of grade 3/4 TRAEs were 43% and 38%, respectively. Serious TRAEs of any grade occurred at respective rates of 31% and 17%; the rates of grade 3/4 serious TRAEs were 27% and 15%, respectively. TRAEs led to treatment discontinuation in 20% of patients in the nivolumab/ipilimumab arm vs 13% of patients in the lenvatinib or sorafenib arm. TRAEs led to death in 3 patients (3%) and 1 patient (<1%), respectively.

In the nivolumab/ipilimumab group, hepatic TRAEs included hepatobiliary disorders (any-grade, 15%; grade 3/4, 12%), increased aspartate aminotransferase (AST) levels (23%; 1%) increased alanine aminotransferase (ALT) levels (18%; 3%), and increased bilirubin levels (11%; 0%). In this group, cardiac TRAEs and hemorrhagic TRAEs were reported at rates of 6% and 3%, respectively; no grade 3/4 cardiac or hemorrhagic TRAEs were noted.

In the control arm, hepatic TRAEs comprised hepatobiliary disorders (any-grade, 6%; grade 3/4, 3%), increased AST levels (16%; 0%) increased ALT levels (10%; <1%), and increased bilirubin levels (17%; 2%). The rates of any-grade cardiac TRAEs and hemorrhagic TRAEs were 51% and 12%, respectively; the respective rates of grade 3/4 cardiac and hemorrhagic TRAEs were 10% and <1%.

Immune-mediated AEs (irAEs) reported in the experimental arm included pneumonitis (5%), hepatitis (14%), rash (23%), hypothyroidism/thyroiditis (22%), hypothyroidism (13%), thyroiditis (10%), and hyperthyroidism (19%). irAEs that led to treatment discontinuation included pneumonitis (n = 1) and hepatitis (n = 2).

References

1. Qin S, Bai Y, Han G, et al. Nivolumab (NIVO) plus ipilimumab (IPI) vs lenvatinib (LEN) or sorafenib (SOR) as first-line (1L) treatment in Chinese patients with unresectable/advanced hepatocellular carcinoma (HCC): CheckMate 9DW expanded analyses. Presented at: 2025 ESMO Gastrointestinal Cancers Congress; July 2-5, 2025; Barcelona, Spain. Abstract 157P.
2. FDA approves nivolumab with ipilimumab for unresectable or metastatic hepatocellular carcinoma. FDA. April 11, 2025. Accessed July 2, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-ipilimumab-unresectable-or-metastatic-hepatocellular-carcinoma

Kim Kardashian reportedly got triggered at the high-profile wedding of Jeff Bezos and Lauren Sanchez.

As per the latest findings of Closer Magazine, the former wife of Kanye West had a meltdown at the wedding event in Italy.

This meltdown was reportedly sparked by the all the attention that Sydney Sweeney garnered from the eligible bachelors.

“Kim won’t say it outright, but seeing Sydney get all the attention in Venice was a huge blow to her ego,” claimed a source.

“She went into the trip with very high hopes, She’s been single for so long, it’s really starting to mess with her confidence,” the insider noted of the single mom, who is reportedly seeking new paramours.

In conclusion, “She still looks incredible, but she’s in her 40s, has four kids, and she worries it’s too much baggage to get the kind of man she wants.”

“She’s not holding it against Sydney, she actually thinks she’s gorgeous and talented, but it’s more that Kim’s realising she’s not the ‘it’ girl anymore, and that’s triggered all her worst insecurities.”

One in 10 cars sold in the UK in June were made in China, according to the latest industry figures.

New Chinese brands such as BYD, Jaecoo and Omoda are growing rapidly in the UK.

There has been a particular surge over the past few months, at a time when most other G7 countries have levied significant extra tariffs against their imports.

Around 18,944 cars made by Chinese-owned brands, including MG and Polestar, were sold in June, which is 10% of overall UK sales, according to the latest figures from the Society of Motor Manufacturers and Traders (SMMT). That is up from 6% in the same month a year ago.

Across the first half of this year, more than 8% – or 1 in 12 – cars sold were Chinese, up from 5% in 2023 and 2024. This was mainly but not exclusively electric vehicles.

By comparison a study by Jato Analytics for the first five months of the year put Chinese brands at 4.3% of the market across the EU, and just 1.6% in Germany and 2.7% in France. Spain was higher though at 9.2%.

Its analyst Felipe Munoz said: “The fact that the UK has not imposed tariffs is a big opportunity for the Chinese, along with the popularity of electric cars.

“MG is also playing like a local brand, and unlike France and Germany, the UK doesn’t have a big local industry to protect.”

However, some industry grandees have warned that the UK industry will struggle to compete, and Britain might have to introduce quotas.

Chinese firms and their franchises have been buying up car showrooms.

“Chinese manufacturers are producing cars which are better, cheaper and more innovative in every sector of the market,” said John Neill, former SMMT President and ex-chief executive of Unipart.

“If they are going to sell here we are going to have to get the Chinese to manufacture here.”

The government has so far faced little pressure from existing suppliers on copying the tariffs imposed by the EU, US, and Canada on electric cars.

The majority of EU member states backed big taxes being imposed on imports of EVs from China, which can be as high as around 45%, and Canada announced its imposition of a 100% tax on Chinese made EVs.

The EU and China are in negotiations to replace the tariff with a minimum price system.

Some Chinese manufacturers are also in the process of opening factories in the EU which could export across Europe including the UK tariff-free.

The SMMT said that one in four buyers of new cars in the UK are now purchasing electric cars – although the transition to electric has been driven by “unsustainable” discounting by manufacturers, says Mike Hawes, the SMMT’s chief executive.

“As we have seen in other countries, government incentives can supercharge the market transition,” he said.

Quantitative vessel tortuosity (QVT), a noninvasive, radiomics-based imaging biomarker, was able to detect the antiangiogenic mechanism of action of fruquintinib (Fruzaqla) in patients with metastatic colorectal cancer (mCRC), according to data from a retrospective analysis of the phase 3 FRESCO-2 trial (NCT04322539) presented during the 2025 ESMO Gastrointestinal Cancer Congress.

Results from the analysis demonstrated that patients in the fruquintinib group experienced a 70% decrease of vessel inflection in lung lesions from baseline to day 1 of cycle 3 (P < .0006). Additionally, patients in the fruquintinib arm experienced median reductions in vessel volume, torsion, curvature, and radius of 25% (P < .006), 15% (P < .05), 10% (P < .05), and 5% (P < .05), respectively, over the same time period. Conversely, patients in the placebo arm experienced a 30% increase in abnormal vessel branching at day 1 of cycle 3 compared with baseline (P < .05).

“Significant changes in QVT features between patients in the fruquintinib and placebo arms were observed during the first assessment, demonstrating the early antiangiogenic action of fruquintinib,” Sara Lonardi, MD, chief of the Oncology 3 Unit of Veneto Institute of Oncology in Padua, Italy, and her coauthors wrote in the poster. “The observed differences in Delta QVT radiomic features…quantify the ability of fruquintinib to prevent the formation of a twisted, heterogeneous vasculature.”

In November 2023, the FDA approved fruquintinib for the treatment of adult patients with mCRC who received previous treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy.² The regulatory decision was partially supported by prior data from FRESCO-2, which demonstrated that patients treated with the VEGFR inhibitor experienced a 34% reduction in the risk of death compared with those who received placebo (HR, 0.66; 95% CI, 0.55-0.80; P < .001).

FRESCO-2 Study Design and Retrospective Analysis Methods

FRESCO-2 was a global, double-blind study that enrolled adult patients with metastatic CRC.³ Patients were required to have experienced disease progression on or have been intolerant to trifluridine/tipiracil (Lonsurf) or regorafenib (Stivarga). Eligible patients also needed to have a body weight of at least 40 kg, an ECOG performance status of 0 or 1, measurable disease per RECIST 1.1 criteria, and an expected survival of over 12 weeks.

Patients were randomly assigned 2:1 to receive fruquintinib (n = 461) or placebo (n = 230) at 5 mg daily, both in combination with best supportive care.¹ Treatment was administered in 28-day cycles for 3 weeks on, 1 week off. Treatment in both arms continued until disease progression or unacceptable toxicity.

The primary end point was overall survival (OS).³ Secondary end points included progression-free survival, objective response rate, disease control rate, duration of response, and safety.

This retrospective analysis included CT scans from 221 patients enrolled in FRESCO-2; 442 lesions were analyzed from 162 patients in the fruquintinib arm and 167 lesions were analyzed from 59 patients in the placebo arm.¹ For each lesion, 909 QVT features were extracted to quantify peritumoral vascularity. The longitudinal change in QVT features was calculated as the percentage change in features from screening to day 1 of cycle 3.

Following CT scan image transfer, image processing and lesion selection occurred, followed by lesion annotation and segmentation. QVT features were then extracted and selected prior to data integration and analysis.

The presence of lung metastases was the primary objective of the retrospective analysis. Notably, primary colorectal lesions were not analyzed due to the high rate of resection prior to screening.

Additional Findings From the Retrospective Analysis

Additional data from the retrospective analysis revealed that a statistically significant difference in Delta QVT with fruquintinib vs placebo was observed in 11 of the 21 preselected QVT features. Treatment with fruquintinib also showed a clear normalizing effect on tumor-associated vasculature in lung metastases. Compared with placebo, treatment with fruquintinib led to decreases in mean vessel curve intensity (P = .02095), mean branch length (P = .04677), number of branches (P = .01460), mean torsion (P = .01939), torsion length-to-distance ratio (P = .00991), number of vessel inflection points (P = .00606), mean vessel radius (P = .01282), and vessel volume (P = .00606).

“These findings establish the value of QVT as a direct measure for fruquintinib-based antiangiogenic activity and support the use of this method as a potential tool to assess treatment effect based on the mechanism of action,” Lonardi and her coauthors wrote in their conclusion. “Further analyses are planned to include liver lesions and a predictive model of OS.”

Disclosures: Lonardi reported being on the advisory boards of Amgen, Merck Serono, Lilly, Servier, AstraZeneca, MSD, Incyte, Daiichi-Sankyo, Bristol Myers Squibb, Astellas, GlaxoSmithKline, Takeda, Bayer, Rottapharm, BeiGene, Nimbus Therapeutics, and Helion. She has also been an invited speaker for Pierre Fabre, GlaxoSmithKline, Roche, Servier, Amgen, Bristol Myers Squibb, incyte, Lilly, Merck Serono, and AstraZeneca, as well as a coordinating primary investigator for Amgen, Merck Serono, Bayer, Roche, Lilly, AstraZeneca, and Bristol Myers Squibb.

References

1. Lonardi S, Yardibi O, Dasari A, et al. A novel imaging biomarker, quantitative vessel tortuosity, captures the antiangiogenic effect of fruquintinib in metastatic colorectal cancer. Presented at: ESMO Gastrointestinal Cancers Congress 2025; July 2-5, 2025; Barcelona, Spain. Abstract 32P.
2. FDA approves fruquintinib in refractory metastatic colorectal cancer. FDA. November 8, 2023. Accessed July 4, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-fruquintinib-refractory-metastatic-colorectal-cancer
3. A study of efficacy and safety of fruquintinib (HMPL-013) in participants with metastatic colorectal cancer (FRESCO-2). ClinicalTrials.gov. Updated April 4, 2025. Accessed July 4, 2025. https://clinicaltrials.gov/study/NCT04322539