Category: 3. Business

Using bioinformatics, researchers identified region-specific biomarkers—FGFR4, FLT1, and WNT5A—that drive distinct tumor behaviors and may serve as diagnostic and therapeutic targets.¹ Additionally, the researchers identified 2 promising drugs, dovitinib and nintedanib, which could enhance precision treatment strategies for patients with colorectal cancer (CRC).

The findings from this analysis are published in BMC Cell Communication and Signaling.

“By integrating bulk-RNA-[sequencing] data with secretome data, we developed an approach that enabled us to infer the process of cellular interaction in CRC through the construction of an interactome,” wrote the researchers of the study. “This analysis revealed the presence of distinct molecular markers depending on the tumor’s site of origin.”

Comprehensive genomic profiling (CGP) is increasingly shaping precision medicine in CRC by revealing how specific genetic alterations influence prognosis and treatment decisions.² Using next-generation sequencing, CGP can analyze hundreds of cancer-related genes and key biomarkers in a single test, helping guide therapy selection, identify actionable mutations, and support enrollment in clinical trials. Although a recent study showed that CGP-guided therapies have not yet yielded significant survival advantage, mutations in TP53 and SMAD4 were linked to poorer outcomes, and PTEN alterations were associated with improved survival. These insights highlight the growing role of CGP in informing personalized CRC care and identifying potential targets for future drug development.

In this study, researchers analyzed gene expression data from the TCGA-COAD database, focusing on tumor location and purity to uncover molecular differences in CRC.¹ Using RNA-seq data, they identified region-specific ligands and receptors based on a reference secretome list, revealing key signaling pathways within the tumor microenvironment. The researchers then built an interactome to visualize these cell-to-cell interactions and pinpoint the most influential genes. Finally, survival analysis and drug susceptibility assessments were performed to evaluate the prognostic potential of these genes and identify candidate drugs for targeted CRC therapy.

Distinct molecular signatures were revealed between right- and left-sided CRCs, highlighting how tumor location influences biological behavior. Through integration of secretome data and interactome analysis, FGFR4, FLT1, and WNT5A emerged as key biomarkers linked to carcinogenesis, fibroblast recruitment, and cell division. These genes demonstrated strong diagnostic and prognostic potential, underscoring their role in tumor progression and treatment response. Importantly, drug analysis identified dovitinib and nintedanib as promising targeted therapies, as both agents interact with multiple biomarkers, offering new opportunities for personalized CRC treatment.

Overall, the researchers believe the study advances understanding of CRC by uncovering region-specific biomarkers that influence tumor behavior and therapeutic response. The identification of FGFR4, FLT1, and WNT5A as key molecular drivers provides a foundation for developing more precise diagnostic tools and personalized treatments. Moreover, the prediction of dovitinib and nintedanib as potential targeted therapies highlights opportunities to enhance treatment efficacy and overcome drug resistance. Together, these findings offer valuable insights into the tumor microenvironment and lay the groundwork for future experimental validation and clinical translation in CRC care.

“Nonetheless, the conclusions are constrained by the absence of experimental validation,” acknowledged the researchers. “Future investigations should incorporate comprehensive in vitro and in vivo studies to substantiate the diagnostic and therapeutic efficacy of these candidate genes and drugs. Such validation is essential to elucidate their mechanistic roles and to advance their clinical application in CRC management.”

References

1. Caxali GH, Aal MCE, Osvaldo CWG, et al. Integrating the secretome and interactome to identify novel biomarkers and therapeutic targets in colorectal cancer. Cell Commun Signal. 2025;23(1):428. doi:10.1186/s12964-025-02424-4

2. Steinzor P. Genomic profiling in colorectal cancer reveals prognostic markers. AJMC^®. September 11, 2025. Accessed October 17, 2025. https://www.ajmc.com/view/genomic-profiling-in-colorectal-cancer-reveals-prognostic-markers

Treatment with the combination of osimertinib (Tagrisso) and platinum-based chemotherapy and pemetrexed led to an improvement in overall survival (OS) compared with osimertinib monotherapy across subgroups of patients with EGFR-mutated non–small cell lung cancer (NSCLC), including those with poor prognostic factors, according to data from an exploratory analysis of the phase 3 FLAURA2 trial (NCT04035486).¹

Previously reported data from the trial’s final OS analysis showed that patients treated with osimertinib plus chemotherapy (n = 279) achieved a median OS of 47.5 months (95% CI, 41.0-not calculable [NC] vs 37.6 months (95% CI, 33.2-43.2) for those treated with osimertinib alone (n = 278; HR, 0.77; 95% CI, 0.61-0.96; P = .02).^1,2

The exploratory analysis, which was presented at the 2025 ESMO Congress, examined outcomes for patients based on the following 6 prognostic factors:¹

• Central nervous system (CNS) metastases (yes vs no)
• Bone metastases (yes vs no)
• Liver metastases (yes vs no)
• EGFR mutation status (exon 21 L858R mutation vs exon 19 deletion)
• TP53 status (altered vs wild-type)
• Plasma EGFR mutations in circulating tumor DNA (ctDNA; detected vs undetected)

• In the trial’s final OS analysis, osimertinib plus chemotherapy yielded a median OS of 47.5 months vs 37.6 month for osimertinib alone.

• An exploratory analysis presented at the 2025 ESMO Congress showed the OS benefit was consistent with osimertinib plus chemotherapy across subgroups, including those with poor prognostic factors.

• Data from FLAURA2 supported the 2024 FDA approval of osimertinib plus chemotherapy for EGFR-mutated advanced NSCLC.

“Hazard ratios for OS favored the combination arm, regardless of baseline prognostic factors, and were consistent with the overall population,” lead study author Pasi A. Jänne, MD, PhD, said in a presentation of the data. Jänne is a senior physician, senior vice president for Translational Medicine, director of the Belfer Center for Applied Cancer Science, director of the Chen-Huang Center for EGFR Mutant Lung Cancers, and the David M. Livingston, MD, Chair at Dana-Farber Cancer Institute, as well as a professor of medicine at Harvard Medical School in Boston, Massachusetts.

What Were the FLAURA2 OS Outcomes by Prognostic Subgroup?

In patients harboring CNS metastases at baseline, the median OS was 40.9 months (95% CI, 35.2-46.6) for osimertinib plus chemotherapy (n = 116) compared with 29.7 months (95% CI, 25.6-35.8) for osimertinib monotherapy (n = 110; HR, 0.72; 95% CI, 0.52-0.99). The 3-year OS rates in this subgroup were 57% (95% CI, 48%-66%) and 40% (95% CI, 31%-49%), respectively. In patients without CNS metastases at baseline, the median OS was not reached (NR; 95% CI, 45.0-NC) for osimertinib plus chemotherapy (n = 163) vs 43.9 months (95% CI, 37.8-53.3) for osimertinib alone (n = 168; HR, 0.77; 95% CI, 0.57-1.05).

Patients harboring EGFR exon 21 L858R mutations treated with osimertinib plus chemotherapy (n = 106) achieved a median OS of 38.1 months (95% CI, 33.4-42.0) vs 32.4 months (95% CI, 28.0-37.6) for osimertinib alone (n = 107; HR, 0.76; 95% CI, 0.55-1.07). The respective 3-year OS rates were 54% (95% CI, 44%-63%) and 42% (95% CI, 32%-51%). In patients harboring EGFR exon 19 deletions, the median OS was NR (95% CI, 47.2-NC) for osimertinib plus chemotherapy (n = 172) vs 43.0 months (95% CI, 35.7-51.9) for osimertinib alone (n = 169; HR, 0.76; 95% CI, 0.56-1.02).

Among patients with EGFR mutations detected in plasma ctDNA, the median OS was 38.4 months (95% CI, 33.2-46.6) for osimertinib plus chemotherapy (n = 148) vs 32.5 months (95% CI, 28.8-35.8) for osimertinib monotherapy (n = 161; HR, 0.79; 95% CI, 0.60-1.03). The 3-year OS rates in this subgroup were 53% (95% CI, 45%-61%) for osimertinib plus chemotherapy vs 42% (95% CI, 35%-50%) for osimertinib alone. In patients without EGFR mutations detected in plasma ctDNA, the median OS was NR (95% CI, 50.8-NC) and NR (95% CI, 46.0-NC) for the combination (n = 65) and osimertinib monotherapy (n = 48), respectively (HR, 0.79; 95% CI, 0.44-1.44).

In the subgroup of patients with liver metastases at baseline, osimertinib plus chemotherapy (n = 43) generated a median OS of 36.6 months (95% CI, 24.4-NC) compared with 28.0 months (95% CI, 21.3-32.5) for osimertinib alone (n = 66; HR, 0.66; 95% CI, 0.41-1.05). The 3-year OS rates were 54% (95% CI, 38%-68%) and 35% (95% CI, 24%-47%), respectively. In patients without liver metastases at baseline, the median OS was 49.6 months (95% CI, 43.0-NC) for osimertinib plus chemotherapy (n = 236) vs 41.8 months (95% CI, 35.7-49.8) for osimertinib alone (n = 212; HR, 0.83; 95% CI, 0.64-1.07).

For patients with bone metastases, the median OS was 40.2 months (95% CI, 33.9-47.2) for osimertinib plus chemotherapy (n = 132) vs 32.3 months (95% CI, 26.7-36.5) for osimertinib monotherapy (n = 142; HR, 0.76; 95% CI, 0.56-1.02). The 3-year OS rates were 55% (95% CI, 46%-63%) and 42% (95% CI, 34%-50%), respectively. In patients without bone metastases, the median OS was NR (95% CI, 46.6-NC) and 44.5 months (95% CI, 38.3-NC) for osimertinib plus chemotherapy (n = 147) and osimertinib alone (n = 136), respectively (HR, 0.79; 95% CI, 0.57-1.10).

Finally, in patients harboring TP53 alterations, those given osimertinib plus chemotherapy (n = 46) experienced a median OS of 51.1 months (95% CI, 35.0-NC) vs 43.1 months (95% CI, 34.0-50.1) for those administered osimertinib alone (n = 40; HR, 0.71; 95% CI, 0.40-1.27). The 3-year OS rates were 65% (95% CI, 49%-77%) and 58% (95% CI, 41%-71%), respectively. In patients with TP53 wild-type disease, the median OS was NR (95% CI, 46.6-NC) for osimertinib plus chemotherapy (n = 33) and NR (95% CI, 41.3-NC) for osimertinib alone (n = 34; HR, 0.70; 0.32-1.54).

How Was the FLAURA2 Trial Designed?

Notably, prior data from this study supported the February 2024 FDA approval of osimertinib plus platinum-based chemotherapy for use in patients with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.³

FLAURA2 enrolled patients at least 18 years of age with previously untreated, pathologically confirmed locally advanced or metastatic nonsquamous NSCLC harboring EGFR exon 19 deletions or exon 21 L858R mutations.¹ Patients were also required to have a World Health Organization performance status of 0 or 1. Patients with stable CNS metastases were allowed to enroll, and brain scans were mandatory at baseline.

Patients were randomly assigned 1:1 to receive osimertinib at 80 mg per day in combination with pemetrexed at 500 mg/m² and carboplatin at area under the curve 5 or cisplatin at 75 mg/m² once every 3 weeks for 4 cycles, followed by osimertinib at 80 mg once per day plus pemetrexed at 500 mg/m² once every 3 weeks as maintenance therapy; or osimertinib alone at 80 mg per day. Treatment beyond disease progression was permitted at investigator discretion.

Investigator-assessed progression-free survival per RECIST 1.1 criteria served as the trial’s primary end point. OS was a key secondary end point.

Disclosures: Jänne reported serving on an advisory board or committee for AstraZeneca, Mirati Therapeutics, Boehringer Ingelheim, Plizer, Roche/Genentech, Chugai, El Lilly, Ignyta, Takeda, Novartis, Voronoi, SFJ Pharmaceuticals, Biocartis, LOXO Oncology, PUMA, Sanofi, Transcenta, Daichi Sankyo, Bayer, Silicon Therapeutics, AbbVie, Monte Rosa, Merus, Allorion Therapeutics, Accutar Biotech, Scorpion Therapeutics, Merus, Frontier Medicines, Hongyun Biotechnology, Duality Biologics, Blueprint Medicines, Dizal Pharmaceuticals, GSK, Tolremo, Myris Therapeutics, and Bristol Myers Squibb; and receiving grants or contracts from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Takeda, PUMA, Astellas Pharmaceuticals, and Daiichi Sankyo. He also is the co-inventor of the Dana-Farber Cancer Institute (DFCI)–owned patent on EGFR mutations licensed to Lab Corp, and he reported royalties on DFCI-owned intellectual property on EGFR mutations licensed to Lab Corp.

References

1. Jänne PA, Planchard D, Kobayashi K, et al. FLAURA2: exploratory overall survival analyses in patients with poorer prognostic factors treated with osimertinib ± platinum-pemetrexed as first-line treatment for EGFR-mutated advanced NSCLC. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA77.
2. Tagrisso plus chemotherapy demonstrated a median overall survival of nearly four years, the longest benefit ever reported in a global Phase III trial in EGFR-mutated advanced lung cancer. News release. AstraZeneca. September 7, 2025. Accessed October 17, 2025. https://www.astrazeneca.com/media-centre/press-releases/2025/tagrisso-plus-chemotherapy-demonstrated-a-median-overall-survival-of-nearly-four-years.html
3. FDA approves osimertinib with chemotherapy with chemotherapy for EGFR-mutated non-small cell lung cancer. FDA. February 16, 2024. Accessed October 17, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-osimertinib-chemotherapy-egfr-mutated-non-small-cell-lung-cancer

By Steve Gelsi and Greg Robb

While the economy seems to be chugging along, the list of possible threats appears to be getting longer as banks clock signs of tariff stress

Fifth Third Bank Chief Executive Tim Spence says his business clients are optimistic about the economy despite uncertainty over tariffs and other unknowns.

Bankers tend to use a variety of data points to gauge the state of the economy, depending on the institution and the individual doing the forecasting. And after this week’s stock-market drop for bank stocks, they’ve scoured every one of them.

Despite the customary optimism from banks as a way to encourage economic activity, this week’s earnings updates revealed that lenders continue to watch for key data points around tariffs impacting client costs, as well as some weakness in certain sectors – such as sluggish home construction and softness in the auto-financing business.

Banks are also increasing their scrutiny of their business-lending activities, after bank stocks sold off this week due to the fallout from high-profile bankruptcies at auto-parts seller First Brands and subprime auto lender Tricolor. But so far, they haven’t reported any alarming rises in delinquent loans, another key metric.

JPMorgan Chase & Co. (JPM) Chief Executive Jamie Dimon raised the possibility of more “cockroaches” in the form of credit problems, which has banks studying their balance sheets.

Fifth Third Bancorp (FITB) Chief Executive Tim Spence summed up the current environment as “nauseous optimism” – a variation on the more common term, “cautious optimism.”

The nauseousness comes from tariff uncertainty that “absolutely continues to weigh” on some clients, he said. It’s a factor in more persistent inflation, which in turn impacts consumer spending and borrowing.

On the other hand, expected interest-rate cuts by the Federal Reserve are providing hope among businesses of improved demand and investment.

Clients that have put off capital improvements are now seeking loans, Spence noted.

“We are getting requests now for financing that are reflected in the pipeline in the middle-market business, in particular, to support that sort of shift from rent to own,” Spence said. “So I think that’s quite positive.”

The bank’s customers in the logistics business function as a “good bellwether” on the economy and have also been somewhat upbeat, he added.

“We’re hearing from logistics clients that there hasn’t exactly been a huge rebound, but that the activity has stabilized and is moving on the upswing,” Spence said, with help from businesses lifted by government infrastructure investments and AI-infrastructure efforts.

On the down side, however, has been residential construction and autos, according to Spence.

Credit problems appear to be idiosyncratic for now

Dimon’s comments about the possibility for more trouble in bank loans came up again Friday on an earnings call for Huntington Bancshares Inc. (HBAN), as the bank reported stronger-than-expected third-quarter earnings.

“I’m obviously aware of Jamie’s comments this week, but I don’t see it broadly affecting the industry, and many of those who reported are suggesting the consumer is in relatively good shape,” said Huntington CEO Stephen Steinour. “We certainly are not seeing forward indicators in terms of delinquency or other measures.”

Bankers this week told MarketWatch that the U.S. economy is so complex, there’s no single indicator that would sum up the outlook for the consumer. Since economic downturns tend to crop up for a variety of reasons, it’s challenging at best to anticipate the most important data point among thousands.

“As we look at the data, we’re not seeing any imminent signs of a recession,” Zach Wasserman, Huntington’s chief financial officer, told MarketWatch. He said the bank uses a battery of both internal and external data to weigh economic strength on the horizon.

Unemployment remains a key macro factor, because if people can’t pay back their loans, banks’ credit will suffer. If more people lose their jobs, it’s widely expected to have a negative impact on bank credit.

To gauge the health of the consumer, banks also look at credit-card spending, as well as interest-rate changes in the U.S. Treasury market and corporate bond markets.

Bank balance sheets tend to benefit when the Treasury yield curve holds on to its historic shape of a steep yield curve. But signs that short-term rates may be dropping sharply could also signal a flattening of the yield curve, which is less favorable for banks.

Loan growth is another key metric, with Huntington Bank now forecasting 2025 loan growth of about 8%, up from its earlier estimate of 6% to 8%.

But questions continue to swirl around problems with collateral that caused Fifth Third to lose money on loans to Tricolor, while other lenders took losses on loans to First Brands.

Asked about banks’ credit strength this week, St. Louis Fed President Alberto Musalem said his understanding is that the credit concerns at regional banks appeared related to individual circumstances, and were not systemic or tied to general macroeconomic conditions.

Also read: Zions takes $50 million loan loss as another credit ‘cockroach’ appears. Regional-bank stocks are falling.

-Steve Gelsi -Greg Robb

This content was created by MarketWatch, which is operated by Dow Jones & Co. MarketWatch is published independently from Dow Jones Newswires and The Wall Street Journal.

  (END) Dow Jones Newswires

  10-17-25 1646ET
Copyright (c) 2025 Dow Jones & Company, Inc.

Introductory Remarks at the IMF’s Western Hemisphere Department Press Briefing

By Rodrigo Valdés, Director of the Western Hemisphere Department
2025 Annual Meetings

October 17, 2025

Over the past months, Latin America and the Caribbean have been navigating through shifting winds of a changing and uncertain global environment. Our Regional Economic Outlook discusses how the region has fared and the challenges ahead. Let me share a few highlights from our report.

Growth in Latin America and the Caribbean has experienced no major disruptions in the first half of 2025. It is projected to remain steady at 2.4 percent in 2025 and moderate slightly next year, with risks tilted to the downside.

Despite uncertainty, global conditions have been broadly supportive:

1. Commodity prices have stabilized after a brief period of volatility;
2. Financial conditions have eased amid declining sovereign spreads and a weaker US dollar; and
3. Regional exports have kept pace with global trends.

Labor markets remained robust, generally supporting private consumption in most economies. Low trade exposure of many economies to the United States and lower tariffs compared with other emerging economies have also provided buffers.

Against this background, macroeconomic policy calibration remains a challenge in several countries. While most countries are expected to strengthen their fiscal positions, structural primary balances are projected to be lower than anticipated, indicating unwelcome delays in fiscal consolidation.

In fact, with public debt ratios rising, fiscal consolidation is increasingly important to mitigate risks of decompression in risk premiums. Insufficient fiscal effort complicates not only debt sustainability but also the effectiveness of monetary policy—I will come back to this later.

On the monetary policy front, inflation remains above target in some countries, amid relatively balanced risks. While robust labor markets and fiscal concerns slow disinflation, recent exchange rate appreciation is helping in some cases.

Central banks have responded appropriately, remaining data driven, and inflation expectations are stable but also remain above targets. Continued caution is warranted, especially in cases where economic slack is not evident and inflation remains above targets.

Looking ahead, the region’s potential growth remains stuck in its low historical average and lagging its peers. This reflects slowing labor force expansion, low capital accumulation, and stagnant productivity.

This year’s report has undertaken two analytical studies to better understand some policy challenges.

One focuses on interactions between monetary and fiscal policies. Reforms to enhance central bank independence have helped achieve price stability. However, high public debt and deficits can constrain monetary policy. To safeguard price stability, countries must focus on advancing fiscal consolidation and improving fiscal frameworks. Lower debt levels make monetary policy more effective, aiding convergence to inflation targets.

The second investigates some drivers of low total factor productivity in the region. Exploring firm-level data, we show that this is partly explained by persistent resource misallocation and sluggish productivity growth among firms. More productive firms face barriers to expand, which calls for reforms to address frictions—including size-based regulations, financial constraints, and limited competition.

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The Fund remains closely engaged with the region through policy advice, capacity development, and financial support.

In terms of program engagement, since April, Barbados completed its arrangement under the Extended Fund Facility and the Resilience and Sustainability Facility, and a new Flexible Credit Line (FCL) has been launched with Costa Rica, while Colombia canceled its FCL.

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To sum up, the global landscape is shifting, but this is no reason for inaction. As the saying goes, countries may not control the winds, but they can adjust their sails. Reinforcing policy frameworks, rebuilding fiscal buffers, and fostering growth opportunities are the sails to adjust.

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Before returning to Julie, let me also remind you that I will be leaving the Western Hemisphere Department by the end of this month, moving to the Fiscal Affairs Department. WHD new director will be Nigel Chalk – sitting here – who already supervises several countries and activities and guarantees a seamless transition.

Unlock the Editor’s Digest for free

Roula Khalaf, Editor of the FT, selects her favourite stories in this weekly newsletter.

Deloitte has agreed to pay $34mn to investors who blamed the auditor for losses stemming from the collapse of one of US’s largest nuclear power projects, a rare legal settlement by a Big Four firm.

Former shareholders in the South Carolina utility Scana said Deloitte failed to spot red flags and allowed management to hide mounting problems with the construction of two nuclear reactors a decade ago.

Scana shares tumbled when it eventually abandoned work on the reactors in 2017, leading to its cut-price sale to a rival utility and jail time for its former chief executive, who pleaded guilty to misleading regulators. The fiasco also pushed construction company Westinghouse into bankruptcy.

Lawyers for Scana’s shareholders claimed Deloitte should pay a portion of losses estimated at $800mn, because the firm repeatedly signed off on financial statements in which the company indicated the project would be finished on time.

A judge will need to approve the settlement, which was filed in South Carolina federal court on Friday, but plaintiff lawyers called it an “excellent result” for shareholders. It comes on top of a $192.5mn settlement from Scana and its officers in 2020.

“The $34mn recovery from Deloitte is one of the largest securities class-action settlements against an auditing firm in the last decade,” the lawyers wrote.

“The settlement was also reached after extensive litigation, at a time when the parties were fully aware of the strengths and weaknesses of their respective positions, and was the culmination of extensive arm’s length negotiations overseen by a well-respected mediator.”

Deloitte on Friday said: “Deloitte stands behind the quality of its audit work and is participating in this settlement to avoid the ongoing cost and distraction of extended litigation.”

Investors face a high legal bar for implicating auditors in the securities frauds of their clients because audits are meant to provide only “reasonable assurance” that financial statements are free of error. In the largest recent settlement, PwC paid $65mn in 2015 over claims related to the collapse of the brokerage MF Global.

Years of litigation shined a harsh spotlight on Deloitte’s audit, particularly how the firm dismissed claims from a Scana whistleblower who said as early as 2015 that the reactors would not be completed in time to trigger vital government subsidies.

One of Deloitte’s own construction experts conducted an internal review of the firm’s work after the fact, and penned a six-page handwritten memo concluding it should have done more to investigate the whistleblower’s claims.

Deloitte has said it stands behind its work and argued in court that Scana’s financial statements contained plenty of warnings about the project’s risks. Its settlement does not indicate an acceptance of liability.

Accolades  |  October 17, 2025

World Tax

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World Tax, the International Tax Review’s annual guide to the world’s leading tax advisory practices, has recognized Gibson Dunn in eight categories in the 2026 editions of its EMEA and APAC guides. The firm was recognized in France – General Corporate Tax; France – Tax Controversy; France – Transactional Tax; Hong Kong – General Corporate Tax; Hong Kong – Private Client; UK – General Corporate Tax; UK – Indirect Tax; and UK – Transactional Tax. Partners Sandy Bhogal, Elaine Chen, Jérôme Delaurière, Ben Fryer, Brian Gilchrist, Sanford Stark, and Jeff Trinklein were also recognized individually in the 2026 edition.

The guides were published on October 16, 2026.

Approval Broadens Indication for TEZSPIRE to a Second Disease Characterized by Epithelial-Driven Inflammation

THOUSAND OAKS, Calif., Oct. 17, 2025 /PRNewswire/ — Amgen (NASDAQ:AMGN) and AstraZeneca today announced that the U.S. Food and Drug Administration (FDA) approved TEZSPIRE^® (tezepelumab-ekko) for the add-on maintenance treatment of inadequately controlled chronic rhinosinusitis with nasal polyps (CRSwNP) in adult and pediatric patients aged 12 years and older. TEZSPIRE is the first and only biologic approved for CRSwNP that targets thymic stromal lymphopoietin (TSLP).

CRSwNP affects up to approximately 320 million people worldwide and is a complex epithelial-driven inflammatory condition characterized by persistent inflammation and benign polyp growths within the nasal cavity.^1-5 People living with CRSwNP commonly experience airflow obstruction and symptoms including congestion and an impaired sense of smell.^1-5 For many patients, current therapies such as systemic and intranasal corticosteroids and repeated sinus surgeries do not offer lasting relief.³

“For people living with CRSwNP, every breath can feel like a struggle, and many endure years of recurring symptoms and surgeries without significant relief. The approval of TEZSPIRE represents a meaningful advance, derived from our longstanding focus on complex inflammatory diseases rooted in epithelial biology,” said Jay Bradner, M.D., executive vice president of Research and Development at Amgen. “This approval is an important step forward for patients who have long needed more durable options that address the root causes of this disease, while establishing the impact of TSLP inhibition beyond asthma.” 

The approval by the Food and Drug Administration (FDA) was based on efficacy and safety data from the WAYPOINT Phase III trial, which were presented at the 2025 American Academy of Allergy Asthma & Immunology (AAAAI)/World Allergy Organization (WAO) Joint Congress and simultaneously published in The New England Journal of Medicine.^6,7 In the trial, TEZSPIRE demonstrated a statistically significant and clinically meaningful reduction in nasal polyp severity and showed near-elimination of the need for surgery and significant reduction in systemic corticosteroid use vs. placebo.

“Over 320 million lives globally are disrupted by chronic rhinosinusitis with nasal polyps. The FDA approval of TEZSPIRE brings forward a new treatment option that has demonstrated rapid and sustained symptom improvement, nearly eliminating the need for future surgeries and significantly reducing systemic steroid use,” said Dr. Joseph Han, Vice Chair of Department of Otolaryngology – Head and Neck Surgery, Old Dominion University, and co-primary investigator of the WAYPOINT trial. “By targeting thymic stromal lymphopoietin (TSLP) at the top of the inflammatory cascade, TEZSPIRE offers a novel option for patients who continue to endure the disruption of this disease despite available treatments.”

“Chronic rhinosinusitis with nasal polyps is a persistent and often-overlooked disease that can significantly impact daily life, robbing patients of their ability to breathe without congestion and full sense of smell,” said Kenneth Mendez, President and CEO of the Asthma and Allergy Foundation of America (AAFA). “This approval introduces an innovative treatment option for patients with the potential to help address the ongoing cycle of debilitating symptoms, surgeries and systemic steroid use.” 

The safety and tolerability profile of TEZSPIRE in the WAYPOINT trial was generally consistent with its established profile in severe asthma.⁶ The most frequently reported adverse events in the trial were COVID-19, nasopharyngitis and upper respiratory tract infection.⁶  

Regulatory applications are currently under review in Europe, China, Japan and several other countries based on the WAYPOINT trial.

TEZSPIRE^® (tezepelumab-ekko) U.S. Indication

TEZSPIRE is indicated for:

• the add-on maintenance treatment of adult and pediatric patients aged 12 years and older with severe asthma. TEZSPIRE is not indicated for the relief of acute bronchospasm or status asthmaticus.
• the add-on maintenance treatment of adult and pediatric patients aged 12 years and older with inadequately controlled chronic rhinosinusitis with nasal polyps (CRSwNP).

TEZSPIRE^® (tezepelumab-ekko) Important Safety Information 

CONTRAINDICATIONS
Known hypersensitivity to tezepelumab-ekko or excipients.

WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions
Hypersensitivity reactions were observed in the clinical trials (e.g., rash and allergic conjunctivitis) following the administration of TEZSPIRE. Postmarketing cases of anaphylaxis have been reported. These reactions can occur within hours of administration, but in some instances have a delayed onset (i.e., days). In the event of a hypersensitivity reaction, consider the benefits and risks for the individual patient to determine whether to continue or discontinue treatment with TEZSPIRE.

Acute Asthma Symptoms or Deteriorating Disease
TEZSPIRE should not be used to treat acute asthma symptoms, acute exacerbations, acute bronchospasm, or status asthmaticus.

Abrupt Reduction of Corticosteroid Dosage
Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with TEZSPIRE. Reductions in corticosteroid dose, if appropriate, should be gradual and performed under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.

Parasitic (Helminth) Infection
It is unknown if TEZSPIRE will influence a patient’s response against helminth infections. Treat patients with pre-existing helminth infections before initiating therapy with TEZSPIRE. If patients become infected while receiving TEZSPIRE and do not respond to anti-helminth treatment, discontinue TEZSPIRE until infection resolves.

Live Attenuated Vaccines 
The concomitant use of TEZSPIRE and live attenuated vaccines has not been evaluated. The use of live attenuated vaccines should be avoided in patients receiving TEZSPIRE.

ADVERSE REACTIONS 
The most common adverse reactions (incidence ≥ 3%) are:

• 
  Asthma: pharyngitis, arthralgia, and back pain.
• 
  Chronic rhinosinusitis with nasal polyps: nasopharyngitis, upper respiratory tract infection, epistaxis, pharyngitis, back pain, influenza, injection site reaction and arthralgia.

USE IN SPECIFIC POPULATIONS 
There are no available data on TEZSPIRE use in pregnant women to evaluate for any drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Placental transfer of monoclonal antibodies such as tezepelumab-ekko is greater during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy.

Please see the full 
 
 Prescribing Information
  including Patient Information and Instructions for Use.

You may report side effects related to AstraZeneca products by clicking 
 
 here
 
 .

About TEZSPIRE^® (tezepelumab-ekko)
TEZSPIRE is a first-in-class human monoclonal antibody that works on the primary source of inflammation: the airway epithelium, which is the first point of contact for viruses, allergens, pollutants and other environmental triggers and insults. Specifically, TEZSPIRE targets and blocks TSLP, a key epithelial cytokine that sits at the top of multiple inflammatory cascades and initiates an overreactive immune response to allergic, eosinophilic and other types of airway inflammation associated with severe asthma.^{8, 9} TSLP is released in response to multiple triggers associated with asthma exacerbations, including allergens, viruses and other airborne particles.^9,10

Expression of TSLP is increased in the airways of patients with asthma and has been correlated with disease severity.^5,8 Blocking TSLP may prevent the release of pro-inflammatory cytokines by immune cells, resulting in the prevention of asthma exacerbations and improved asthma control.^8,9,11

TEZSPIRE is currently approved as a pre-filled, single-use pen and auto-injector for self-administration for the treatment of severe asthma in the U.S., Europe, Japan, and more than 60 countries across the globe,^12-15 and for the treatment of chronic rhinosinusitis with nasal polyps in the U.S. 

Beyond severe asthma and CRSwNP, TEZSPIRE is also in development for other potential indications including chronic obstructive pulmonary disease (COPD) and eosinophilic esophagitis (EoE).^16,17 In October 2021, tezepelumab was granted Orphan Drug Designation by the FDA for the treatment of EoE. 

About Chronic Rhinosinusitis with Nasal Polyps (CRSwNP [nasal polyps]) 
CRSwNP is a complex inflammatory disorder characterized by persistent inflammation of the nasal mucosa accompanied by benign growths, called nasal polyps.^2,3 Nasal polyps can block nasal passages and lead to breathing problems, difficulty in sense of smell, nasal discharge, and other adverse effects on quality of life.^1,4,5

Epithelial dysfunction and inflammation are important characteristics of chronic rhinosinusitis and impede the ability of the epithelium to act as a physical and immunological barrier against the external environment.¹⁸ Estimates suggest that up to 56% of patients with CRSwNP have comorbid asthma. Thymic stromal lymphopoietin (TSLP) is an epithelial cytokine that has been implicated in shared pathophysiological processes underlying severe asthma and CRSwNP.^19,20

Current treatments for CRSwNP include intranasal and/or systemic corticosteroids, surgery and biologic medication.^3,5,21-26

About the Phase 3 WAYPOINT Trial  
WAYPOINT was a double-blind, multi-center, randomized, placebo-controlled, parallel group trial designed to evaluate the efficacy and safety of tezepelumab in adults with uncontrolled CRSwNP.^6,7,27 Participants received tezepelumab or placebo, administered via subcutaneous injection. The trial also included a post-treatment follow-up period of 12-24 weeks for participants who completed the 52-week treatment period.^6,7,27   

The co-primary endpoints of the trial, were change from baseline in total nasal polyp size, measured by the endoscopic total Nasal Polyp Score, and change from baseline in bi-weekly mean nasal congestion, measured by the participant reported Nasal Congestion Score evaluated as part of the daily Nasal Polyposis Symptom Diary.^6,27 Key secondary endpoints included loss of smell; improvement in disease specific health-related quality of life as measured by SinoNasal Outcome Test (SNOT-22) score; Lund-Mackay score; time to surgery decision and/or systemic corticosteroids for nasal polyposis; time to nasal polyposis surgery decision; time to systemic corticosteroids for nasal polyposis; Nasal Polyposis Symptom Diary total symptom score and, in the population with co-morbid asthma, pre-bronchodilator FEV1 at Week 52.^6,27

About the Amgen and AstraZeneca Collaboration
In 2020, Amgen and AstraZeneca updated the 2012 collaboration agreement for TEZSPIRE. Both companies will continue to share costs and profits equally after payment by AstraZeneca of a mid-single-digit royalty to Amgen. AstraZeneca continues to lead development and Amgen continues to lead manufacturing. All aspects of the collaboration are under the oversight of joint governing bodies. Under the amended agreement, in North America, Amgen, as the principal, recognizes product sales of TEZSPIRE in the United States, and AstraZeneca, as the principal, recognizes product sales of TEZSPIRE in Canada. AstraZeneca leads commercialization for TEZSPIRE outside North America.

About Amgen 
Amgen discovers, develops, manufactures and delivers innovative medicines to help millions of patients in their fight against some of the world’s toughest diseases. More than 40 years ago, Amgen helped to establish the biotechnology industry and remains on the cutting-edge of innovation, using technology and human genetic data to push beyond what’s known today. Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases. 

In 2024, Amgen was named one of the “World’s Most Innovative Companies” by Fast Company and one of “America’s Best Large Employers” by Forbes, among other external recognitions. Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average^®, and it is also part of the Nasdaq-100 Index^®, which includes the largest and most innovative non-financial companies listed on the Nasdaq Stock Market based on market capitalization.

For more information, visit Amgen.com and follow Amgen on X, LinkedIn, Instagram, YouTube and Threads.

Amgen Forward-Looking Statements
This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including any statements on the outcome, benefits and synergies of collaborations, or potential collaborations, with any other company (including BeOne Medicines Ltd. or Kyowa Kirin Co., Ltd.), the performance of Otezla® (apremilast), our acquisitions of ChemoCentryx, Inc. or Horizon Therapeutics plc (including the prospective performance and outlook of Horizon’s business, performance and opportunities, and any potential strategic benefits, synergies or opportunities expected as a result of such acquisition), as well as estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes, effects of pandemics or other widespread health problems on our business, outcomes, progress, and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission reports filed by Amgen, including our most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Unless otherwise noted, Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.

No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future. Even when clinical trials are successful, regulatory authorities may question the sufficiency for approval of the trial endpoints we have selected. We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify safety, side effects or manufacturing problems with our products, including our devices, after they are on the market.

Our results may be affected by our ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments involving current and future products, sales growth of recently launched products, competition from other products including biosimilars, difficulties or delays in manufacturing our products and global economic conditions, including those resulting from geopolitical relations and government actions. In addition, sales of our products are affected by pricing pressure, political and public scrutiny and reimbursement policies imposed by third-party payers, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment. Furthermore, our research, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and foreign government regulatory authorities. Our business may be impacted by government investigations, litigation and product liability claims. In addition, our business may be impacted by the adoption of new tax legislation or exposure to additional tax liabilities. Further, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors, or we may fail to prevail in present and future intellectual property litigation. We perform a substantial amount of our commercial manufacturing activities at a few key facilities, including in Puerto Rico, and also depend on third parties for a portion of our manufacturing activities, and limits on supply may constrain sales of certain of our current products and product candidate development. An outbreak of disease or similar public health threat, and the public and governmental effort to mitigate against the spread of such disease, could have a significant adverse effect on the supply of materials for our manufacturing activities, the distribution of our products, the commercialization of our product candidates, and our clinical trial operations, and any such events may have a material adverse effect on our product development, product sales, business and results of operations. We rely on collaborations with third parties for the development of some of our product candidates and for the commercialization and sales of some of our commercial products. In addition, we compete with other companies with respect to many of our marketed products as well as for the discovery and development of new products. Further, some raw materials, medical devices and component parts for our products are supplied by sole third-party suppliers. Certain of our distributors, customers and payers have substantial purchasing leverage in their dealings with us. The discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations. Our efforts to collaborate with or acquire other companies, products or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful. There can be no guarantee that we will be able to realize any of the strategic benefits, synergies or opportunities arising from the Horizon acquisition, and such benefits, synergies or opportunities may take longer to realize than expected. We may not be able to successfully integrate Horizon, and such integration may take longer, be more difficult or cost more than expected. A breakdown, cyberattack or information security breach of our information technology systems could compromise the confidentiality, integrity and availability of our systems and our data. Our stock price is volatile and may be affected by a number of events. Our business and operations may be negatively affected by the failure, or perceived failure, of achieving our sustainability objectives. The effects of global climate change and related natural disasters could negatively affect our business and operations. Global economic conditions may magnify certain risks that affect our business. Our business performance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase our common stock. We may not be able to access the capital and credit markets on terms that are favorable to us, or at all.

CONTACT: Amgen, Thousand Oaks George Shea, 202-531-7364 (media)Elissa Snook, 609-251-1407 (media)Adam Elinoff, 805-313-9775 (investors) 

REFERENCES

1. Stevens WW, et al. Chronic Rhinosinusitis with Nasal Polyps. J Allergy Clin Immunol Pract. 2016; 4 (4): 565-572.   
2. Bachert C, et al. Phenotypes and Emerging Endotypes of Chronic Rhinosinusitis. J Allergy Clin Immunol Pract. 2016; 4 (4): 621-628.  
3. Del Toro E, Portela J. Nasal Polyps. [Updated 2023 Jul 31]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560746/ [Last accessed: August 2025].  
4. Abdalla S, et al. Prevalence of sinonasal outcome test (SNOT-22) symptoms in patients undergoing surgery for chronic rhinosinusitis in the England and Wales National prospective audit. Clin Otolaryngol. 2012; 37 (4): 276-282.   
5. Chen S, et al. Systematic literature review of the epidemiology and clinical burden of chronic rhinosinusitis with nasal polyposis. Curr Med Res Opin. 2020;36(11):1897-1911.  
6. Lipworth, BJ, Han JK, et al. Tezepelumab in adults with severe, uncontrolled CRSwNP. N Engl J Med. 2025.   
7. Lipworth, BJ, Han JK, et al. Efficacy and safety of tezepelumab in adults with severe chronic rhinosinusitis with nasal polyps: results from the Phase 3 WAYPOINT Study. [Late breaking oral presentation]. Presented at the American Academy of Allergy, Asthma & Immunology/World Allergy Organization Joint Congress 2025 (28 February – 03 March).   
8. Corren J, et al. Tezepelumab in adults with uncontrolled asthma. N Engl J Med. 2017;377:936-946.    
9. Varricchi G, et al. Thymic Stromal Lymphopoietin Isoforms, Inflammatory Disorders, and Cancer. Front Immunol. 2018;9:1595.  
10. Menzies-Gow A, et al. Tezepelumab in Adults and Adolescents with Severe, Uncontrolled Asthma. N Engl J Med. 2021;384:1800-1809.  
11. Li Y, et al. Elevated Expression of IL-33 and TSLP in the Airways of Human Asthmatics In Vivo: A Potential Biomarker of Severe Refractory Disease. J Immunol. 2018; 200: 2253–2262.
12. TEZSPIRE (tezepelumab) US prescribing information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761224s003lbl.pdf. [Last accessed: August 2025].      
13. TEZSPIRE (tezepelumab) Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/tezspire-epar-product-information_en.pdf. [Last accessed: August 2025].   
14. AstraZeneca plc. TEZSPIRE approved in Japan for the treatment of severe asthma. Available at: https://www.astrazeneca.com/media-centre/press-releases/2022/tezspire-approved-in-japan-for-severe-asthma.html. [Last accessed: August 2025].     
15. Data on File. AstraZeneca. 2024. REF-251231.
16. Clinicaltrials.gov. Tezepelumab COPD Exacerbation Study (COURSE) [Online]. Available at: https://clinicaltrials.gov/ct2/show/NCT04039113. [Last accessed: August 2025].  
17. Clinicaltrials.gov. Efficacy and Safety of Tezepelumab in Patients with Eosinophilic Esophagitis (CROSSING). Available at: https://clinicaltrials.gov/study/NCT05583227?rank=1. [Last accessed: August 2025].  
18. Wynne M, et al. Contribution of epithelial cell dysfunction to the pathogenesis of chronic rhinosinusitis with nasal polyps. Am J Rhinol Allergy. 2019;33:782–790.  
19. Laidlaw TM, et al. Chronic Rhinosinusitis with nasal polyps and asthma.  J Allergy Clin Immunol Pract 2021;9:1133–1141.
20. Liao B, et al. Interaction of thymic stromal lymphopoietin, IL-33, and their receptors in epithelial cells in eosinophilic chronic rhinosinusitis with nasal polyps. Allergy. 2015;70:1169–1180.
21. Xolair (omalizumab) Summary of Product Characteristics; Available at: https://www.ema.europa.eu/en/documents/product-information/xolair-epar-product-information_en.pdf. [Last accessed: August 2025].    
22. Xolair (omalizumab) US prescribing information; Available at: https://www.gene.com/download/pdf/xolair_prescribing.pdf. [Last accessed: August 2025].  
23. Nucala (mepolizumab) Summary of Product Characteristics. Available at: https:// www.ema.europa.eu/en/documents/product-information/nucala-epar-product-information_en.pdf. [Last accessed: August 2025].  
24. Nucala (mepolizumab) US prescribing information; Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761122s006,125526s018lbl.pdf. [Last accessed: August 2025].     
25. Dupixent (dupilumab) Summary of Product Characteristics. Available at: https://www.ema.europa.eu/en/documents/product-information/dupixent-epar-product-information_en.pdf. [Last accessed: August 2025].  
26. Dupixent (dupilumab) US prescribing information; Available at: https://www.regeneron.com/downloads/dupixent_fpi.pdf. [Last accessed: August 2025].  
27. Clinicaltrials.gov. Efficacy and Safety of Tezepelumab in Participants With Severe Chronic Rhinosinusitis With Nasal Polyposis (WAYPOINT). Available at: https://clinicaltrials.gov/ct2/show/NCT04851964. [Last accessed: August 2025].  

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SOURCE Amgen

Adjuvant ribociclib (Kisqali) in combination with a nonsteroidal aromatase inhibitor (AI) displayed a durable benefit in terms of invasive disease–free survival (iDFS) compared with an AI alone (n = 2552) in patients with hormone receptor–positive, HER2-negative early breast cancer (HR, 0.716; 95% CI, 0.618-0.829; 1-sided P < .0001), according to data from the 5-year prespecified analysis of the phase 3 NATALEE trial (NCT03701334) presented during the 2025 ESMO Congress.¹

The median follow-up was 55.4 months. The 36-month iDFS rates in the ribociclib (n = 2594) and AI-alone (n = 2552) arms were 90.8% and 88.0%, respectively; the 60-month iDFS rates were 85.5% and 81.0%, respectively.

Sidebar: Phase 3 NATALEE Trial 5-Year Outcomes: Key Takeaways

• The NATALEE trial examined adjuvant ribociclib plus a nonsteroidal AI vs an AI alone in patients with hormone receptor–positive, HER2-negative early breast cancer.

• The regimen was previously approved by the FDA in September 2024 for the treatment of patients with hormone receptor–positive, HER2-negative stage II and III early breast cancer at high risk of recurrence, including those with node-negative disease.

• Findings from the 5-year analysis of NATALEE revealed that patients who received ribociclib plus an AI experienced a significant invasive disease–free survival benefit compared with those treated with an AI alone (HR, 0.716; 95% CI, 0.618-0.829; 1-sided P < .0001).

“Ribociclib plus an AI continues to reduce the risk of recurrence beyond a 3-year treatment window, supporting its use as adjuvant therapy in a broad population of patients with hormone receptor–positive, HER2-negative early breast cancer at high risk of recurrence,” John Crown, MD, a professor and consultant medical oncologist at St. Vincent’s University Hospital in Dublin, Ireland, said during the presentation.

Notably, in September 2024, the FDA approved adjuvant ribociclib in combination with an AI for the treatment of patients with hormone receptor–positive, HER2-negative stage II and III early breast cancer at high risk of recurrence, including those with node-negative disease.² The regulatory decision was supported by prior data from NATALEE.

What Were the Design Features of NATALEE?

NATALEE was an open-label, multicenter, randomized trial that enrolled adult patients with stage II and III hormone receptor–positive, HER2-negative early breast cancer.¹ Patients were permitted to have received prior endocrine therapy up to 12 months before enrollment.

Patients with anatomical stage IIA disease needed to have N0 disease that was grade 2 and had evidence of high risk, defined by a Ki-67 score of at least 20%, an Oncotype DX Breast Recurrence Score of at least 26 or high-risk status via genomic risk profiling, and grade 3 disease; patients with N1 disease in this anatomical stage were also eligible. Patients with anatomical stage IIB disease needed to have N0 or N1 disease. Patients with anatomical stage III disease could have N0 through N3 disease.

Eligible patients were randomly assigned 1:1 to receive ribociclib at 400 mg per day via a 3-weeks-on, 1-week-off dosing schedule for 3 years in combination with a nonsteroidal AI for at least 5 years, or a nonsteroidal AI alone.

The primary end point was iDFS using Standardized Definitions for Efficacy End Points criteria. Secondary end points included relapse-free survival, distant disease–free survival (DDFS), overall survival, patient-reported outcomes, safety and tolerability, and pharmacokinetic measures. Distant recurrence–free survival, as well as gene expression and alterations in circulating tumor (ct) DNA/ctRNA samples, were also evaluated as exploratory end points.

At the May 28, 2025, data cutoff, 62.8% of patients in the combination arm had completed 3 years of treatment with ribociclib, and 36.5% of patients had completed 5 years of AI therapy. AI treatment was ongoing in 27.1% of patients, and 51.4% of patients remained in the follow-up phase.

In the AI-alone arm, 34.4% of patients had completed 5 years of treatment. Therapy was ongoing in 23.7% of patients, and 50.3% of patients were in the follow-up phase.

What Were the Safety and Additional Efficacy Data From NATALEE?

At the time of this analysis, all patients had stopped receiving therapy for a median of 2 years. No new safety signals were identified with ribociclib, including no delayed toxicities or cumulative effects following therapy. Since the previous 4-year exploratory analysis, with an additional follow-up of 12.9 months, 3 patients had died in the combination arm due to adverse effects (AEs), and 2 others had died in the control arm due to AEs. Three percent of patients had developed secondary primary malignancies in the control arm compared with 2.7% of those in the combination arm.

At a median follow-up of 56.5 months, the 5-year OS rates in the investigational and control arms were 94.1% vs 92.5%, respectively (HR, 0.800; 95% CI, 0.637-1.003; 1-sided P = .026). At a median follow-up of 55.5 months, a significant benefit in terms of DDFS was reported in favor of the ribociclib arm (HR, 0.709; 95% CI, 0.608-0.827). A similar benefit in terms of DRFS was also observed in favor of the investigational arm (HR, 0.699; 95% CI, 0.594-0.824).

Patients experienced an iDFS benefit with the addition of ribociclib to an AI vs an AI alone, irrespective of having N0 (ribociclib arm, n = 285; control arm, n = 329; HR, 0.606; 95% CI, 0.372-0.986) or N-positive (ribociclib arm, n = 2261; control arm, n = 2218; HR, 0.737; 95% CI, 0.631-0.860) nodal status. Notably, an iDFS benefit with ribociclib was reported across all prespecified patient subgroups.

“For the first time, in this 5-year analysis, a clinically meaningful risk reduction of approximately 30% was seen for DDFS or death and DRFS or death. Ribociclib plus an AI showed a continued numerical trend for improved OS,” Crown emphasized in his conclusion.

Disclosures: Crown reported receiving personal fees from Pierre Fabre, Immunocore, Novartis, AstraZeneca, and Regeneron; owning stock with Oncoassure and Akkure; and receiving travel support to meetings from Novartis, MSD Oncology, Pfizer, Roche, AstraZeneca, and Regeneron.

References

1. Crown J, Stroyakovskii D, Yardley D, et al. Adjuvant ribociclib plus nonsteroidal aromatase inhibitor therapy in patients with HR+/HER2– early breast cancer: NATALEE 5-year outcomes. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA14.
2. FDA approves Novartis Kisqali to reduce risk of recurrence in people with HR+/HER2- early breast cancer. News release. Novartis. September 17, 2024. Accessed October 17, 2025. https://www.novartis.com/news/media-releases/fda-approves-novartis-kisqali-reduce-risk-recurrence-people-hrher2-early-breast-cancer