The OncFive: Top Oncology Articles for the Week of 12/14

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 T-DXd Plus Pertuzumab for HER2+ Breast Cancer

The FDA approved fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) paired with pertuzumab (Perjeta) as first-line treatment for patients with unresectable or metastatic HER2-positive breast cancer. The decision was based on findings from the phase 3 DESTINY-Breast09 trial (NCT04784715), in which the median progression-free survival (PFS) with T-DXd plus pertuzumab (n = 383) was 40.7 months (95% CI, 36.5-not estimable [NE]) vs 26.9 months (95% CI, 21.8-NE) with trastuzumab (Herceptin), pertuzumab, and a taxane (n = 387; HR, 0.56; 95% CI, 0.44-0.71; P <.0001). The confirmed objective response rate (ORR) was 87% (95% CI, 83%-90%) with T-DXd/pertuzumab compared with 81% (95% CI, 77%-85%) in the control arm. Overall survival (OS) data were immature at the time of analysis.

FDA Approves Subcutaneous Amivantamab for EGFR+ NSCLC

The FDA cleared amivantamab and hyaluronidase-lpuj (Rybrevant Faspro), a subcutaneous formulation, for all approved indications of amivantamab-vmjw (Rybrevant) in EGFR-mutant non–small cell lung cancer. The approval was supported by data from the phase 3 PALOMA-3 trial (NCT05388669), which demonstrated noninferior pharmacokinetics for subcutaneous (n = 206) vs intravenous (IV; n = 212) amivantamab when combined with lazertinib (Lazcluze). The ORR was 30% (95% CI, 24%-37%) with subcutaneous dosing vs 33% (95% CI, 26%-39%) with IV dosing. The median PFS was 6.1 months (95% CI, 4.3-8.1) vs 4.3 months (95% CI, 4.1-5.7), respectively. The median OS favored the subcutaneous formulation at 12.9 months (95% CI, 12.9-NE) vs NE (95% CI, 10.2-NE), with IV therapy (HR, 0.62; 95% CI, 0.42-0.92; nominal P = .02).

FDA Grants Full Approval to Rucaparib for BRCA Mutation–Associated mCRPC

The FDA granted traditional approval to rucaparib (Rubraca) for patients with BRCA mutation–associated metastatic castration-resistant prostate cancer previously treated with an androgen receptor–directed therapy. The decision was based on findings from the phase 3 TRITON3 trial (NCT02975934), in which rucaparib (n = 201) improved median radiographic PFS to 11.2 months (95% CI, 9.2-13.8) vs 6.4 months (95% CI, 5.4-8.3) with physician’s choice of therapy (n = 101; (HR, 0.50; 95% CI, 0.36-0.69; P < .0001). The median OS was 23.2 months (95% CI, 19.1-25.2) with rucaparib vs 21.2 months (95% CI, 18.0-23.1) with physician’s choice. Exploratory analyses indicated that the rPFS benefit was primarily driven by patients with BRCA mutations rather than ATM alterations.

FDA Awards National Priority Voucher to Teclistamab Plus Daratumumab in R/R Myeloma

The regulatory agency awarded a Commissioner’s National Priority Voucher to teclistamab-cqyv (Tecvayli) plus daratumumab (Darzalex) for patients with relapsed/refractory multiple myeloma. The voucher was supported by findings from the phase 3 MajesTEC-3 trial (NCT05083169), in which median PFS was not reached with teclistamab plus daratumumab (n = 291) vs 18.1 months with daratumumab plus pomalidomide (Pomalyst) or bortezomib (Velcade) and dexamethasone (n = 296; HR, 0.17; 95% CI, 0.12-0.23; P < .0001). The ORR was 89.0% with teclistamab plus daratumumab vs 75.3% in the control arm (odds ratio [OR], 2.65; 95% CI, 1.68-4.18; P <.0001), with complete response or better rates of 81.8% vs 32.1% (OR, 9.56; 95% CI, 6.47-14.14; P < .0001). The median OS was not reached in either arm, but favored teclistamab plus daratumumab (HR, 0.46; 95% CI, 0.32-0.65; P < .0001).

Perioperative Enfortumab Vedotin/Pembrolizumab Meets EFS, OS, pCR End Points in Cisplatin-Eligible MIBC

Perioperative pembrolizumab (Keytruda) plus enfortumab vedotin-ejfv (Padcev) significantly improved event-free survival vs neoadjuvant chemotherapy and surgery in cisplatin-eligible patients with muscle-invasive bladder cancer in the phase 3 KEYNOTE-B15/EV-304 trial (NCT04700124). An interim analysis also met key secondary end points of OS and pathologic complete response. The safety profile was consistent with known toxicities of the individual agents, with no new safety signals reported. Results are planned for presentation at an upcoming medical meeting and submission to global regulatory authorities.