The OncFive: Top Oncology Articles for the Week of 4/26

Welcome to OncLive®’s OncFive!

Every week, we bring you a quick roundup of the 5 top stories from the world of oncology—ranging from pivotal regulatory decisions to key pipeline updates to expert insights on breakthroughs that are moving the needle in cancer care. This resource is designed to keep you informed on the latest updates in the space, in just a matter of minutes.

Here’s what you may have missed this week:

FDA Approves Vepdegestrant for ER+/HER2– Advanced Breast Cancer With an ESR1 Mutation

The FDA has approved vepdegestrant (Veppanu) for use in adult patients with estrogen receptor–positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression after at least 1 line of endocrine therapy, as detected by an FDA-authorized test. The decision was supported by findings from the phase 3 VERITAC-2 trial (NCT05654623), in which patients with ESR1 mutations treated with vepdegestrant (n = 136) experienced a median progression-free survival (PFS) of 5.0 months (95% CI, 3.7–-7.4) vs 2.1 months (95% CI, 1.9-3.5) with fulvestrant (Faslodex; n = 134; HR, 0.57; 95% CI, 0.42-0.77; P = .0001). The overall response rates (ORRs) in the respective arms were 19% (95% CI, 12%-27%) vs 4% (95% CI, 1.6%-10%). Any-grade treatment-emergent adverse effects (TEAEs) occurred in 87% of vepdegestrant-treated patients vs 81% of those treated with fulvestrant. The most common any-grade TEAEs included fatigue (27% vs 16%), elevated alanine aminotransferase (ALT) levels (14% vs 10%), elevated aspartate aminotransferase (AST) levels (14% vs 10%), and nausea (13% vs 9%). Overall survival (OS) data from VERITAC-2 were immature at the time of data cutoff.

FDA ODAC Votes Against Clinical Benefit of Switching to Camizestrant in HR+ Breast Cancer After ESR1 Mutation Detection

The FDA's Oncologic Drugs Advisory Committee (ODAC) voted 6 to 3 that switching to camizestrant upon emergence of an ESR1 mutation during treatment with an aromatase inhibitor (AI) and a CDK4/6 inhibitor, ahead of radiographic disease progression, did not demonstrate clinically meaningful benefit in patients with hormone receptor–positive, HER2-negative metastatic breast cancer, based on data from the phase 3 SERENA-6 trial (NCT04964934). Updated findings shared during the 2025 San Antonio Breast Cancer Symposium indicated that switching to camizestrant plus a CDK4/6 inhibitor such as palbociclib (Ibrance), ribociclib (Kisqali), or abemaciclib (Verzenio; n = 157) led to a median PFS of 16.6 months (95% CI, 14.7-19.4) vs 9.2 months (95% CI, 7.2-9.7) with continued AI plus CDK4/6 inhibitor therapy (n = 158; HR, 0.46; 95% CI, 0.34-0.62; P < .00001). Although the committee acknowledged the PFS benefit, the FDA expressed concerns that time to second progression (PFS2) was not an acceptable efficacy end point given the trial design, that OS data remain immature, and that potential cardiac adverse effects (AEs) with camizestrant, particularly in combination with ribociclib, warrant careful consideration. A new drug application seeking approval of camizestrant in combination with a CDK4/6 inhibitor for this biomarker-driven indication remains under FDA review. Several committee members emphasized enthusiasm for the oral SERD class while emphasizing the need for stronger evidence to fundamentally shift the current treatment paradigm.

FDA ODAC Votes in Favor of Risk:Benefit Profile of Capivasertib Plus Abiraterone in PTEN-Deficient mHSPC

The FDA's ODAC voted 7 to 1, with 1 abstention, that the benefit of adding capivasertib (Truqap) to abiraterone acetate (Zytiga) outweighs the risk in patients with PTEN-deficient metastatic hormone-sensitive prostate cancer (mHSPC), based on data from the phase 3 CAPItello-281 trial (NCT04493853). Published data from CAPItello-281 showed that patients treated with capivasertib plus abiraterone (n = 507) had a median radiographic PFS (rPFS) of 33.2 months (95% CI, 25.8-44.2) vs 25.7 months (95% CI, 22.0-29.9) with abiraterone plus placebo (n = 505; HR, 0.81; 95% CI, 0.66-0.98; P = .034). A more pronounced benefit was observed in those with 100% PTEN deficiency (median rPFS, 34.1 months vs 22.1 months; HR, 0.68). Grade 3 or higher adverse effects (AEs) occurred in 67.0% vs 40.4% of patients in the respective arms, with notably higher rates of diarrhea (51.9% vs 8.0%), hyperglycemia (38.0% vs 12.9%), and rash (35.4% vs 7.0%) with capivasertib/abiraterone. The regulatory agency raised concerns about the clinical meaningfulness of the rPFS benefit and the high toxicity burden, although committee members noted that capivasertib could address an unmet need for patients with PTEN-deficient mHSPC who are ineligible for or decline chemotherapy. A supplemental new drug application (sNDA) seeking approval of capivasertib in combination with abiraterone for this indication is currently under FDA review.

FDA Green Lights Expanded Access Protocol for Daraxonrasib in Pretreated Metastatic PDAC

The regulatory agency issued a “safe to proceed” letter to Revolution Medicines within 2 days of receiving an expanded access protocol (EAP) request approved April 30, 2026, permitting the use of daraxonrasib (RMC-6236) for patients with previously treated metastatic pancreatic ductal adenocarcinoma (PDAC). This decision follows findings from the first interim analysis of the phase 3 RASolute 302 trial (NCT06625320), in which daraxonrasib led to a median OS of 13.2 months vs 6.7 months with standard chemotherapy in the intention-to-treat (ITT) population (HR, 0.40; P < .0001), with all PFS and OS end point data considered final. Full data are planned for presentation at the 2026 ASCO Annual Meeting. Additional phase 1/2 first-line data from the GI-102 platform study (NCT06445062) shared during the 2026 AACR Annual Meeting showed an ORR of 58% (95% CI, 41%-73%), a disease control rate of 90% (95% CI, 76%-97%), and 6-month PFS and OS rates of 84% (95% CI, 68%-93%) and 90% (95% CI, 76%=96%), respectively, with daraxonrasib plus gemcitabine and nab-paclitaxel (Abraxane; n = 40). Daraxonrasib previously received FDA breakthrough therapy designation, orphan drug designation, and a national priority voucher for previously treated metastatic PDAC harboring KRAS G12 mutations, and Revolution Medicines has announced its intention to submit a new drug application (NDA) under the Commissioner's National Priority Voucher pilot program.

FDA Grants Priority Review to Zanidatamab-Based Regimens in First-Line HER2+ GEA

The FDA has accepted and granted priority review to the supplemental biologics license application for zanidatamab-hrii (Ziihera) plus chemotherapy plus or minus tislelizumab (Tevimbra) for adult patients with HER2-positive unresectable locally advanced or metastatic gastric cancer, gastroesophageal junction (GEJ) cancer, or esophageal adenocarcinoma (GEA) in the first-line setting. A Prescription Drug User Fee Act target action date has been set to August 25, 2026. The application is supported by findings from the phase 3 HERIZON-GEA-01 trial (NCT05152147), in which zanidatamab plus tislelizumab and chemotherapy (n = 302) led to a median PFS of 12.4 months (95% CI, 9.8-18.5) vs 8.1 months (95% CI, 7.0-8.9) with trastuzumab (Herceptin) plus chemotherapy (n = 308; HR, 0.63; 95% CI, 0.51-0.78; P < .0001) and a median OS of 26.4 months (95% CI, 21.5-30.3) vs 19.2 months (95% CI, 16.8-21.8; HR, 0.72; 95% CI, 0.57-0.90; P = .0043). Confirmed ORRs in patients with measurable disease were 70.7% (95% CI, 65%-76%) with zanidatamab plus tislelizumab and chemotherapy and 69.6% (95% CI, 63.9%-75%) with zanidatamab plus chemotherapy; the respective median DORs were 20.7 months (95% CI, 12.6-37.7) and 14.3 months (95% CI, 11.5-21.9). Grade 3 or higher treatment-related adverse effects (TRAEs) were reported in 71.8% of patients in the zanidatamab/tislelizumab arm vs 59.6% of those in the trastuzumab arm, with diarrhea being the most common TRAE across arms.

Honorable Mentions

• The FDA has accepted a NDA for zipalertinib for the treatment of patients with locally advanced or metastatic non–small cell lung cancer with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy, with or without amivantamab-wmjw (Rybrevant).
• A NDA seeking the approval of varegacestat (AL102) for the treatment of adult patients with desmoid tumors has been submitted to the regulatory agency.
• Single-agent elranatamab-bcmm (Elrexfio) led to a statistically significant and clinically meaningful improvement in PFS vs standard-of-care daratumumab (Darzalex) plus pomalidomide (Pomalyst) and dexamethasone (DPd) in patients with relapsed/refractory multiple myeloma who received at least 1 previous line of therapy, meeting the primary end point of the phase 3 MagnetisMM-5 trial (NCT05020236).
• Tovecimig (CTX-009) plus paclitaxel showed a statistically significant improvement in PFS vs chemotherapy alone in patients with previously treated advanced biliary tract cancers, meeting a key secondary end point of the phase 2/3 COMPANION-002 trial (NCT05506943).