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:
DESTINY-Lung04 Outcomes at WCLC 2026: Julia Rotow, MD
Julia Rotow, MD, of Dana-Farber Cancer Institute, reports subgroup and post-progression findings from the phase 3 DESTINY-Lung04 trial (NCT05048797) of first-line fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) in HER2-mutant metastatic non–small cell lung cancer (NSCLC), presented at the IASLC 2026 World Conference on Lung Cancer (WCLC). The trial randomly assigned patients with previously untreated HER2-mutant metastatic NSCLC to receive T-DXd or platinum plus pemetrexed and pembrolizumab (Keytruda), and the median progression-free survival (PFS) was 14.3 months with T-DXd vs 8.3 months with chemoimmunotherapy (HR, 0.63). The median overall survival (OS) ranged from 29 months to 33 months across both arms, and the interim OS analysis did not reach statistical significance, with approximately 93% of patients harboring HER2 exon 20 mutations. Rotow noted that prespecified subgroup analyses consistently favored T-DXd and that the control arm performed better than expected, with PFS outcomes resembling those of the overall population of the phase 3 KEYNOTE-189 trial (NCT02578680). She added that post-progression therapy was substantially imbalanced, as T-DXd and HER2 TKIs became available during the trial and created de facto crossover, in which patients in the control arm more often received subsequent HER2-directed treatment.
Efficacy and Safety of Dibotatug in LGLL: Tapan M. Kadia, MD
Tapan M. Kadia, MD, of The University of Texas MD Anderson Cancer Center, details updated results from a phase 1/2 trial (NCT05475925) evaluating the anti-CD94 antibody dibotatug (DR-01) in patients with large granular lymphocytic leukemia (LGLL). The agent is administered intravenously on days 1, 8, and 15 of cycle 1, followed by maintenance dosing every 28 days, and infusion-related reactions (IRRs) occurred in 17% of patients, predominantly with the first dose. Kadia noted that IRRs were mostly grade 2 or lower, and that headache and fatigue were the most common residual adverse effects (AEs) after the addition of steroid premedication and a graded first-cycle dose. Among evaluable patients who reached the first response assessment (n = 45), the overall response rate (ORR) was approximately 60%, including a complete response rate of approximately 40% under stringent criteria requiring an absolute neutrophil count greater than 1500/µL, hemoglobin levels of at least 11 g/dL, and platelet counts of at least 100,000/µL. Kadia added that these outcomes compare favorably with the approximately 40% response rate historically achieved with single-agent immunosuppressive therapies, such as cyclosporine, methotrexate, and cyclophosphamide, in this setting.
Efficacy of Relacorilant Plus Nab-Paclitaxel in Ovarian Cancer: Lucy Gilbert, MD, MSc
Lucy Gilbert, MD, MSc, of McGill University Health Centre, reviews data from the phase 3 ROSELLA trial (NCT05257408) evaluating the selective glucocorticoid receptor antagonist relacorilant (Lifyorli) plus nab-paclitaxel (Abraxane) vs nab-paclitaxel monotherapy in patients with platinum-resistant ovarian cancer. The dual primary end points were PFS and OS, and in the primary analysis, the combination produced a 30% improvement in median PFS (HR, 0.70; 95% CI, 0.54-0.91; P = .0076) and reduced the risk of death by 35% (HR, 0.65; 95% CI, 0.51-0.83; P = .0004). Gilbert noted that the main toxicities were comparable between the arms and included neutropenia, nausea, and gastrointestinal symptoms, with similar treatment discontinuation rates. An updated analysis presented at the 2026 ASCO Annual Meeting showed that the OS benefit favored the relacorilant combination across all prespecified patient subgroups defined by prior taxane use, including hazard ratios of 0.60 (95% CI, 0.31-1.15) and 0.66 (95% CI, 0.51-0.86) by taxane-free intervals of 6 months or less and longer than 6 months, respectively. She added that the final safety profile remained consistent with the primary analysis, with no new safety signals, no relacorilant-related fatal AEs, and no cases of adrenal insufficiency.
KRAS G12C Survival Signal With Cemiplimab in EMPOWER-Lung 1: David R. Gandara, MD
David R. Gandara, MD, of UC Davis Comprehensive Cancer Center, presents a genomic analysis of the phase 3 EMPOWER-Lung 1 trial (NCT03088540) at WCLC 2026, which randomly assigned patients with advanced NSCLC with PD-L1 expression of at least 50% and no EGFR, ALK, or ROS1 aberrations to receive cemiplimab (Libtayo) or platinum-based chemotherapy. Among 89 patients with KRAS-mutant tumors, cemiplimab improved the median OS vs chemotherapy (HR, 0.46; 95% CI, 0.26-0.83) and the median PFS (HR, 0.31; 95% CI, 0.18-0.54), with ORRs of 67% vs 15%, respectively. KRAS G12C mutations accounted for 44% of these mutations, and in that patient subgroup, the median OS was not reached vs 8 months (HR, 0.18; 95% CI, 0.07-0.49), and the respective ORRs were 74% vs 13%. Gandara noted that response to cemiplimab was unaffected by TP53 co-mutation status and that KRAS G12C tracks with tobacco carcinogenesis and is the most neoantigenic KRAS variant. He added that future trials pairing checkpoint inhibitors with novel agents, including RAS(ON) inhibitors, will need to account for KRAS G12C in their design.
Distinctions Between Proliferative and Cytopenic Myelofibrosis: Gabriela S. Hobbs, MD
Gabriela S. Hobbs, MD, of Massachusetts General Hospital, outlines the factors that distinguish proliferative myelofibrosis from cytopenic myelofibrosis and how these phenotypes inform risk stratification in newly diagnosed disease. Hobbs noted that risk scores, such as the Dynamic International Prognostic Scoring System (DIPSS), which can be applied at the initial visit, and the Mutation-Enhanced International Prognostic Scoring System, which is incorporated once genetic testing returns, have long used cytopenias as markers of higher-risk disease. She explained that proliferative disease typically presents with high white blood cell counts, normal hemoglobin levels, and normal or elevated platelet counts, often with larger spleens and more constitutional symptoms, and frequently arises from essential thrombocythemia or polycythemia vera that has evolved into secondary myelofibrosis. Cytopenic disease, by contrast, typically presents with low blood counts, often lacks splenomegaly or prominent systemic symptoms, and is more likely to harbor mutations beyond JAK2, CALR, and MPL. Hobbs concluded that recognizing the phenotype early, together with the DIPSS framework, helps predict the disease course and tailor management, as patients with low blood counts generally fall into higher-risk categories.
