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 Camizestrant for ESR1-Mutated Breast Cancer: Erica L. Mayer, MD, MPH
Erica L. Mayer, MD, MPH, of Dana-Farber Cancer Institute and Harvard Medical School, unpacked the September 2026 FDA accelerated approval of camizestrant (Etcamah) plus a CDK4/6 inhibitor in the form of abemaciclib (Verzenio), palbociclib (Ibrance), or ribociclib (Kisqali) for use in adult patients with hormone receptor–positive, HER2-negative locally advanced or metastatic breast cancer harboring an emergent ESR1 mutation during aromatase inhibitor (AI) plus CDK4/6 inhibitor therapy, detected by the Guardant360 CDx companion diagnostic. The decision was supported by the phase 3 SERENA-6 trial (NCT04964934), in which switching to camizestrant improved median progression-free survival (PFS) to 16.0 months (95% CI, 12.7-18.2) vs 9.2 months (95% CI, 7.2-9.5) with continued AI plus CDK4/6 inhibitor (HR, 0.44; 95% CI, 0.31-0.60; P < .00001), alongside delays in time to second progression, time to chemotherapy, and quality of life deterioration. A key innovation of SERENA-6 was the use of serial circulating tumor DNA (ctDNA) monitoring during frontline therapy to detect emergent ESR1 mutations in real time, enabling a switch to camizestrant at the time of molecular progression rather than waiting for radiographic or clinical progression. Mayer concluded that beyond offering an effective oral option for those whose cancers acquire ESR1 resistance mutations, the approval introduced ctDNA-guided monitoring as a new treatment paradigm with the potential to improve patient outcomes.
Significance of the FDA Approval of Rusfertide for Polycythemia Vera: Andrew Kuykendall, MD
Andrew Kuykendall, MD, of Moffitt Cancer Center, detailed the clinical significance of the FDA approval of rusfertide (Mimrylo) for adults with polycythemia vera (PV), emphasizing its potential to give patients greater autonomy over hematocrit management. The decision was supported by findings from the phase 3 VERIFY trial (NCT05210790), in which 76.9% of patients who received rusfertide (n = 147) achieved a clinical response vs 32.9% of those who received placebo (n = 146; P < .0001), with hematocrit maintained below 45% in 62.6% vs 14.4% of patients, respectively. Because rusfertide can be self-administered, Kuykendall noted the therapy may reduce dependence on frequent office visits for phlebotomy while also addressing fatigue. He underscored that fatigue is a major driver of impaired quality of life in PV that patients experience more directly than the reduction in thrombotic risk that phlebotomy is intended to provide. He concluded that rusfertide's development was shaped by patient feedback and characterized its approval as a win for the PV community.
Updated Data From MELT-MM With Mezigdomide and Elranatamab in Multiple Myeloma: Ja Min Byun, MD, PhD
Ja Min Byun, MD, PhD, of Seoul National University College of Medicine and Seoul National University Hospital, highlighted updated results from part 1 of the investigator-initiated phase 1b/2 MELT-MM trial (NCT06645678) examining the cereblon E3 ligase modulator mezigdomide plus the BCMA-targeting bispecific antibody elranatamab (Elrexfio) in patients with relapsed/refractory multiple myeloma, presented at the 2026 International Myeloma Society Annual Meeting, noting the combination was designed to reverse T-cell exhaustion driven by sustained exposure to T-cell engagers. Among the 13 efficacy-evaluable patients across the 0.3-mg and 0.6-mg mezigdomide cohorts, the combination achieved an objective response rate (ORR) of 100% and a stringent complete response rate of 92.3%, with a median time to response of 17 days and 90.9% of evaluable patients achieving minimal residual disease negativity at the 10⁻⁵ threshold. The safety profile was consistent with other BCMA-containing regimens: neutropenia (84.6%) and fatigue (84.6%) were the most common adverse effects, and 6 of 13 patients developed an infection, 4 of whom had grade 3 or 4 events. Byun also reported that correlative analyses supported the mechanism—mezigdomide sustained elranatamab-driven T-cell activation, reversed TIGIT and PD-1 upregulation, and did not increase cytokine release syndrome risk—and noted that a randomized phase 2 expansion is now enrolling in Singapore and South Korea.
AI-Designed BCMA/FcRL5-Targeting TRiTE in Multiple Myeloma: Jessica Encinas Mayoral, PhD
Jessica Encinas Mayoral, PhD, of Dana-Farber Cancer Institute, reviewed preclinical data on CB101, an artificial intelligence–optimized BCMA x FcRL5 x CD3 trispecific antibody designed to retain activity against myeloma cells that have lost BCMA expression, and described the rationale for selecting FcRL5 over GPRC5D as a BCMA-partner antigen to avoid the oral, skin, and nail toxicities associated with talquetamab (Talvey). In antigen-knockdown experiments, CB101 retained cytotoxic activity when FcRL5 expression was restored in BCMA-deficient cells while the benchmark BCMA-targeting bispecific teclistamab (Tecvayli) did not; the lead candidate was identified through an artificial intelligence–driven, cytotoxicity-based screening strategy rather than conventional binding-affinity approaches, iterating across multiple selection rounds. For context, Encinas Mayoral pointed to ramantamig (JNJ-79635322), a BCMA x GPRC5D x CD3 trispecific antibody that consolidates the teclistamab/talquetamab combination into a single molecule. In a phase 1 trial (NCT05652335) presented at the 2025 ASCO Annual Meeting, ramantamig produced a 100% ORR and a cytokine release syndrome rate of 56.5%, with no grade 3 or higher events, in BCMA- and GPRC5D-naive patients at the recommended phase 2 dose (n = 27). She noted no direct comparison of ramantamig with the teclistamab/talquetamab combination has been conducted, so relative toxicity profiles remain unclear; however, she suggested a single dual-targeting molecule may prove more practical than administering 2 separate agents.
How to Approach Continuous vs Fixed-Duration Frontline Therapy in CLL: Mary Ann Anderson, MBBS, FRACP, FRCPA, PhD
Mary Ann Anderson, MBBS, FRACP, FRCPA, PhD, of Royal Melbourne Hospital, Peter MacCallum Cancer Centre, and the Walter and Eliza Hall Institute, addressed the tradeoffs between continuous BTK inhibitor–based therapy and time-limited BCL-2 inhibitor–based therapy for patients with treatment-naive chronic lymphocytic leukemia (CLL), noting each approach carries distinct considerations in tolerability, resistance, and long-term sequencing. Continuous BTK inhibitor therapy is straightforward to initiate but carries risks of hypertension, atrial fibrillation, and bleeding, making it less suitable for patients on anticoagulation or with cardiovascular comorbidities. Time-limited venetoclax (Venclexta)-based regimens require slow ramp-up with monitoring for tumor lysis syndrome but allow patients who relapse to do so off therapy, where they are less likely to harbor on-target resistance mutations and can often be retreated with a BTK or BCL-2 inhibitor. Anderson noted that progression on indefinite BTK inhibitor therapy is frequently driven by on-target resistance mutations, and while pirtobrutinib (Jaypirca) can rescue patients who progress on a covalent BTK inhibitor like acalabrutinib (Calquence) or zanubrutinib (Brukinsa) the reverse is not true; she proposed that total PFS from a line of therapy, combining first-line PFS with time to second progression after subsequent treatment, is a more meaningful comparator than PFS on a continuous BTK inhibitor alone. Anderson concluded that the choice between continuous and time-limited frontline CLL therapy is a genuinely complex clinical decision requiring individualization based on patient comorbidities, goals, and the long-term sequencing horizon.
