Five Under 5: Top Oncology Videos for the Week of 11/1

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:

Divarasib vs Sotorasib or Adagrasib in KRAS G12C–Mutated NSCLC: Ferdinandos Skoulidis, MD, PhD, MRCP

Ferdinandos Skoulidis, MD, PhD, MRCP, of The University of Texas MD Anderson Cancer Center, detailed findings from the phase 3 Krascendo 1 trial (NCT06497556), which compared divarasib with sotorasib (Lumakras) or adagrasib (Krazati) in patients with previously treated KRAS G12C–mutated non-small cell lung cancer. In data presented at the 2026 ESMO Congress and published in The New England Journal of Medicine, median progression-free survival (PFS) was 9.8 months with divarasib (n = 167) vs 5.7 months with sotorasib or adagrasib (n = 171; HR, 0.58; 95% CI, 0.44-0.76; P < .0001), with benefit consistent across subgroups, including patients with prior central nervous system metastases, baseline liver metastases, or KEAP1-mutated tumors. At the first interim analysis, median overall survival was 17.7 months vs 12.0 months, respectively (HR, 0.56; 95% CI, 0.41-0.78; P = .0005). Grade 3 or 4 treatment-related adverse effects (TRAEs) occurred in 24.6% vs 34.5% of patients, and TRAEs led to discontinuation in 4.8% vs 11.7%. Gastrointestinal effects such as diarrhea (66% vs 38%) and nausea (53% vs 20%) were more common with divarasib but were mostly grade 1, whereas hepatotoxicity was less frequent and no QT prolongation or pneumonitis was reported with divarasib.

Development Strategies for B7-H4–Directed ADCs in Gynecologic Cancers: Shannon N. Westin, MD, MPH, FACOG

Shannon N. Westin, MD, MPH, FACOG, of The University of Texas MD Anderson Cancer Center, outlined development strategies for B7-H4–directed antibody-drug conjugates (ADCs) in gynecologic cancers, contrasting enrollment regardless of target expression with selection above a predefined expression cut point. In the phase 1 BEHOLD-1 trial (NCT06431594), mocertatug rezetecan (GSK5733584) produced a confirmed objective response rate (ORR) of 62% (95% CI, 46.5%-76.2%) in platinum-resistant ovarian cancer at 5.8 mg/kg (n = 45) and 67% (95% CI, 35%-90%) in endometrial cancer at 4.8 mg/kg (n = 12), with responses observed across a range of B7-H4 expression levels. Puxitatug samrotecan (AZD8205) was being evaluated in B7-H4–selected endometrial cancer in the phase 3 BLUESTAR-Endometrial01 trial (NCT07044336), and Westin noted that a B7-H4–directed ADC could replace the chemotherapy partner in regimens such as that used in the phase 3 DUO-E trial (NCT04269200). Although she favored biomarker-directed strategies, she said testing may be unnecessary when a target is highly expressed. She added that these agents may cause less mucositis and fatigue than other ADCs, and that their topoisomerase I inhibitor payloads may help overcome PARP inhibitor resistance and act synergistically with immunotherapy.

Efficacy and Safety of QTX3034-Based Combinations in KRAS G12D–Mutated CRC: Ignacio Garrido-Laguna, MD, PhD, MBA

Ignacio Garrido-Laguna, MD, PhD, MBA, of Moffitt Cancer Center, reviewed phase 1 data (NCT06227377) presented at the 2026 ESMO Congress for QTX3034, an oral G12D-preferring KRAS inhibitor, plus cetuximab (Erbitux) with or without mFOLFOX6 in KRAS G12D–mutated colorectal cancer, a combination that received FDA fast track designation. The ORR was 50% with the triplet among 10 evaluable patients—most of whom had previously received oxaliplatin—including 1 complete response (CR) in a chemotherapy-naive patient, vs 25% with no CRs among 20 evaluable patients who received the doublet. Grade 3 or higher TRAEs occurred in 24% of patients receiving the doublet vs 43% of those receiving the triplet at 1200 mg twice daily, and dose reductions were required in 14% vs 29%, respectively. No patients discontinued the triplet due to toxicity, and most TRAEs were grade 1 or 2. Garrido-Laguna cautioned against cross-trial comparisons with INCB161734 plus cetuximab, which produced an ORR of 36% in heavily pretreated patients, and noted that larger cohorts are needed.

Potential Role of GPRC5D-Targeted CAR T-Cell Therapy in Myeloma: Doris Hansen, MD

Doris Hansen, MD, of Moffitt Cancer Center, highlighted GPRC5D as a target distinct from BCMA for CAR T-cell therapy in multiple myeloma, noting that as quadruplet regimens move to the frontline and BCMA-directed agents move into earlier relapses, more patients will become quadruple-class exposed and refractory. In a first-in-human phase 1 study (NCT04674813) presented at the 2024 ASH Annual Meeting and Exposition, the GPRC5D-directed CAR T-cell therapy arlocabtagene autoleucel (BMS-986393) produced an ORR of 87% among efficacy-evaluable patients (n = 79), a CR rate of 53%, and a median PFS of 18.3 months (95% CI, 11.8-21.9). The phase 2 registrational QUINTESSENTIAL trial (NCT06297226) met its primary end point of ORR in patients with quadruple-class–exposed relapsed/refractory multiple myeloma who had received at least 4 prior lines of therapy, as well as key secondary end points including CR rate. Hansen added that defining cure was a central theme at the 23rd International Myeloma Society Annual Meeting, and that GPRC5D-directed CAR T-cell therapy may contribute to that goal.

Selecting Patients for BCG Plus Durvalumab in High-Risk NMIBC: Suzanne B. Merrill, MD

Suzanne B. Merrill, MD, of Colorado Urology, addressed patient selection for bacillus Calmette-Guérin (BCG) plus durvalumab (Imfinzi) in BCG-naive, high-risk non-muscle-invasive bladder cancer, drawing on subgroup analyses from the phase 3 POTOMAC trial (NCT03528694) presented at the 2026 ESMO Congress. She said patients with high-grade T1 disease appeared to derive greater benefit from the combination than the overall BCG-naive, high-risk population. Merrill identified high-grade T1 disease with lymphovascular invasion, variant histology, and persistent high-grade T1 disease on repeat transurethral resection as features that may inform selection. She noted that clinicians should also weigh patient preference and the potential for additional adverse effects with the combination. "For BCG and durvalumab, I would consider looking at that combination therapy in your high-risk patients," Merrill said.