The OncFive: Top Oncology Articles for the Week of 9/21

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 Imlunestrant for ER+, HER2-Negative, ESR1-Mutated Metastatic Breast Cancer

The FDA has cleared imlunestrant (Inluriyo) for the treatment of adult patients with estrogen receptor (ER)–positive, HER2-negative advanced or metastatic breast cancer harboring ESR1 mutations who experienced disease progression after at least 1 previous line of endocrine therapy. The Guardant360 CDx assay was also approved as a companion diagnostic to identify those eligible for the drug. The decision was based on data from the phase 3 EMBER-3 trial (NCT04975308), in which imlunestrant (n = 138) reduced the risk of progression or death by 38% vs endocrine therapy (n = 118) in patients with ESR1-mutated disease, yielding a median progression-free survival (PFS) of 5.5 months vs 3.8 months, respectively. Among those with measurable disease, the overall response rate (ORR) was 14.3% with imlunestrant (n = 112) vs 7.7% with endocrine therapy (n = 91). Most adverse effects were grade 1/2, with the most common including decreased hemoglobin, musculoskeletal pain, diarrhea, fatigue, and nausea.

FDA Grants Priority Review to First-Line T-DXd Plus Pertuzumab in Metastatic HER2+ Breast Cancer

The FDA granted priority review to a supplemental biologics license application (sBLA) seeking approval of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) paired with pertuzumab (Perjeta) for frontline use in adults with unresectable or metastatic HER2-positive breast cancer, with a decision expected in the first quarter of 2026. The sBLA is supported by the phase 3 DESTINY-Breast09 trial (NCT04784715), in which T-DXd plus pertuzumab (n = 383) reduced the risk of disease progression or death by 44% vs a taxane plus trastuzumab and pertuzumab (THP; n = 387); the median PFS was 40.7 months vs 26.9 months, respectively. The confirmed ORR was 85.1% with the T-DXd combination vs 78.6% with THP, including complete responses in 15.1% vs 8.5% of patients, respectively. The toxicity profile of the combination was consistent with known toxicities, with no new safety signals observed.

FDA Removes REMS Program for Vandetanib for Medullary Thyroid Cancer

The FDA has removed the Risk Evaluation and Mitigation Strategies (REMS) program for vandetanib (Caprelsa), which has been approved since 2011 for patients with medullary thyroid cancer whose disease is unresectable or metastatic. Vandetanib was originally approved with REMS requirements because of the risk of QT prolongation and fatal arrhythmias. After more than a decade of postmarketing surveillance, no cases of Torsades de pointes or unexplained sudden deaths were reported in US patients treated with the drug, and clinical data showed no consistent safety concerns. Based on these findings, the regulatory agency determined that the REMS program is no longer necessary, noting that clinicians now routinely monitor and manage cardiac risks in practice. The drug remains available under its current prescribing information without additional REMS-specific requirements.

IberDd Demonstrates Positive Topline Efficacy in Relapsed/Refractory Multiple Myeloma

Data from a planned interim analysis of the phase 3 EXCALIBER-RRMM trial (NCT04975997) indicated that iberdomide in combination with daratumumab (Darzalex) and dexamethasone (IberDd) significantly improved minimal residual disease (MRD) negativity rates vs daratumumab, bortezomib (Velcade), and dexamethasone in patients with relapsed/refractory multiple myeloma. The study will continue as planned to evaluate PFS, overall survival (OS), and safety, with Bristol Myers Squibb expected to share the data with health authorities. EXCALIBER-RRMM is a 2-stage, randomized, open-label trial done in adults with 1 to 2 prior lines of therapy. Stage 1 of the trial established 1.0 mg of iberdomide as the recommended dose. In stage 2, approximately 664 patients were randomly assigned to receive IberDd or DVd. The trial’s dual primary end points are MRD negativity and PFS, with key secondary end points of OS, ORR, duration of response, and quality of life.

Giredestrant Plus Everolimus Meets Coprimary PFS End Points in Post–CDK Inhibitor ER+/HER2– Breast Cancer

The investigational all-oral combination of giredestrant plus everolimus (Afinitor) significantly improved progression-free survival (PFS) vs standard-of-care (SOC) endocrine therapy plus everolimus in patients with ER-positive, HER2-negative, locally advanced or metastatic breast cancer who had prior exposure to a CDK4/6 inhibitor, meeting both co-primary end points in the phase 3 evERA Breast Cancer study (NCT05306340). OS data remain immature, but a positive trend favoring the investigational arm was reported, and follow-up will continue. The regimen was well tolerated, with no new safety signals. evERA is the first positive phase 3 trial to evaluate a selective estrogen receptor degrader–containing regimen vs a SOC combination. Roche shared plans to present the data at an upcoming medical meeting and submit findings to health authorities.

Honorable Mentions:

• Myeloma Experts Summarize Key Themes From the 22nd Annual IMS Meeting and Exposition: At the 22nd Annual International Myeloma Society Meeting and Exposition, experts shared the latest on moving anti-BCMA therapies, bispecific antibodies, and CAR T-cell treatments into earlier lines of care, with trial data showing encouraging responses. Sign up to access the full recap for expert insights on treatment sequencing, patient stratification, and strategies to broaden therapy access.
• Breast Cancer Experts: Key ADC Developments and CDK 4/6 Inhibitor Updates Set to Dominate ESMO 2025: As anticipation builds for the 2025 ESMO Congress, antibody-drug conjugates and new approaches for hormone receptor–positive breast cancer, such as CDK4/6 inhibitors combined with PI3K/mTOR inhibitors, are already generating buzz. This exclusive preview features insights from 4 leading breast cancer experts on these late-breaking data, long-term CDK4/6 benefits, and research that could reshape treatment strategies across early and metastatic disease.