Welcome to The Five Under 5, your go-to roundup of the top 5 videos of the week.
These short videos are designed for busy oncologists to view on the go, and feature expert insights on breaking news, regulatory updates, practice-changing data shared at medical meetings, and other key topics in the realm of oncology.
Here's what you may have missed:
FDA Approval of Vusolimogene Oderparepvec-wtpg Plus Nivolumab in Melanoma: Michael Wong, MD, PhD, FRPC
Michael Wong, MD, PhD, FRPC, of Roswell Park Comprehensive Cancer Center, examines the FDA accelerated approval of vusolimogene oderparepvec-wtpg (Tudriqev) in combination with nivolumab (Opdivo) for adult patients with unresectable advanced cutaneous melanoma who progressed on a PD-1–blocking antibody-based regimen. This decision fills a critical gap in the post–PD-1–refractory setting, where tumor-infiltrating lymphocyte (TIL) therapy has been the only FDA-approved option, but TIL therapy’s complexity limits its applicability to carefully selected patients at specialized centers, according to Wong. In contrast, vusolimogene oderparepvec plus nivolumab offers a less resource-intensive approach that does not require hospitalization or intensive supportive care, potentially extending access to a broader population of patients with immunotherapy-refractory disease, he said. Wong concluded that although careful patient selection will remain important, this decision expands the treatment landscape for those who are not suitable candidates for TIL therapy.
FDA Approval of Lutetium Lu 177 Vipivotide Tetraxetan in PSMA+ mHSPC: Michael J. Morris, MD
Michael J. Morris, MD, of Memorial Sloan Kettering Cancer Center, sheds light on the July 2026 FDA approval of lutetium Lu 177 vipivotide tetraxetan (Pluvicto) plus an androgen receptor pathway inhibitor (ARPI) for the treatment of adult patients with prostate-specific membrane antigen (PSMA)–positive metastatic hormone-sensitive prostate cancer (mHSPC). He noted that with this decision, the expanding therapeutic landscape now encompasses multiple biomarker-driven strategies. For those with BRCA2 mutations, abiraterone acetate and niraparib (Akeega) is already cleared in the United States; the phase 3 TALAPRO-3 trial (NCT04821622) has generated interest in talazoparib (Talzenna) for tumors with homologous recombination repair (HRR) gene alterations; and patients with PTEN-altered disease may be candidates for androgen deprivation therapy (ADT) plus an ARPI and capivasertib (Truqap). Morris emphasized that identifying which patients derive the greatest benefit from each approach—including PSMA-targeted radioligand therapy, HRR-directed agents, or docetaxel-based regimens—is a critical research priority, and that multidisciplinary collaboration among medical oncologists, nuclear medicine physicians, and radiation oncologists is essential for individualized treatment planning. He concluded that generating robust comparative data and refining biomarker-driven selection will be key to optimizing outcomes as the number of effective treatment options in mHSPC continues to grow.
FDA Approval of Gedatolisib Plus Fulvestrant ± Palbociclib in PIK3CA Wild-Type Breast Cancer: Adam M. Brufsky, MD, PhD
Adam M. Brufsky, MD, PhD, of the University of Pittsburgh School of Medicine and the University of Pittsburgh Medical Center Hillman Cancer Center, highlights the significance of the FDA approval of gedatolisib (Revtorpyk) plus fulvestrant (Faslodex), with or without palbociclib (Ibrance), for adult patients with hormone receptor (HR)–positive, HER2-negative advanced breast cancer without a PIK3CA mutation who progressed on at least 1 line of endocrine therapy (ET) in the metastatic setting. Supported by the PIK3CA wild-type cohort of the phase 3 VIKTORIA-1 trial (NCT05501886), the regimen demonstrated a median progression-free survival (PFS) of 9.3 months (95% CI, 7.2-16.6) with the triplet and 7.4 months (95% CI, 5.5-9.9) with the doublet vs 2.0 months (95% CI, 1.8-2.3) with fulvestrant alone (HR for triplet vs fulvestrant, 0.24; 95% CI, 0.17-0.35; P < .0001; HR for doublet vs fulvestrant, 0.33; 95% CI, 0.24-0.48; P < .0001). From a safety standpoint, mucositis was the primary toxicity of concern, though treatment discontinuation rates due to adverse effects (AEs) were low due to prompt dose reductions, and gedatolisib was not associated with the severe rash or hyperglycemia seen with alpelisib (Piqray), capivasertib (Truqap), or inavolisib (Itovebi). Brufsky concluded that this approval represents a meaningful advance in a setting with limited options, with intravenous administration as its primary limitation.
FcRH5 as a Therapeutic Target in Multiple Myeloma: Adam D. Cohen, MD
Adam D. Cohen, MD, of the Hospital of the University of Pennsylvania and the Abramson Cancer Center, explores FcRH5 as a therapeutic target in multiple myeloma and the mechanism of action of the investigational bispecific antibody cevostamab (RG6160). FcRH5 is nearly ubiquitously expressed on plasma cells and myeloma cells, with limited expression in normal tissue, resulting in a clean safety profile. Its expression is independent of BCMA and GPRC5D, meaning cells that lose those antigens are expected to retain FcRH5 as a targetable vulnerability. Cevostamab simultaneously binds CD3 on T cells and FcRH5 on myeloma cells to facilitate T-cell–mediated killing; in the phase 1 trial (NCT03275103), single-agent cevostamab in 323 heavily pretreated patients experienced an objective response rate (ORR) of 42.1% and a very good partial response (VGPR) or better rate of 21.5%, rising to an ORR of 44.3% and VGPR or better rate of 25.7% at the recommended phase 2 dose of 160 mg per day (n = 167). Cohen concluded that FcRH5’s favorable expression pattern and independence from other established targets make it a compelling therapeutic option, particularly for patients who have exhausted BCMA- and GPRC5D-directed therapies.
Understanding Mechanisms of Resistance to DLL3-Directed BiTEs in SCLC: Noura Choudhury, MD
Noura Choudhury, MD, of the University of Chicago Medicine, addresses how resistance mechanisms to tarlatamab-dlle (Imdelltra) could inform treatment sequencing in small cell lung cancer (SCLC), as discussed at the Bridging the Gaps in Lung Cancer meeting. The mechanistic basis of resistance has direct clinical implications: if tumors lose DLL3 expression at progression, pivoting to a DLL3-targeted antibody-drug conjugate (ADC) would be counterproductive. Conversely, if DLL3 expression is retained but T-cell functional capacity is lost, that scenario represents an ideal opportunity to shift to an ADC-based approach. Choudhury noted that current understanding of resistance mechanisms remains limited, relying largely on circulating tumor cell data rather than tissue, which underscores the need for tissue-based studies to better define optimal treatment sequencing. She concluded that these insights could also inform the potential for rechallenge with tarlatamab, but robust tissue-based evidence will be essential to translate mechanistic understanding into clinical practice.
