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 Vepdegestrant for ESR1-Mutated, ER+ Advanced Breast Cancer: Kelly E. McCann, MD, PhD
Kelly Elizabeth McCann, MD, PhD, of the University of California San Diego, examines the clinical significance of the FDA approval of vepdegestrant (Veppanu) for adult patients with estrogen receptor (ER)–positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer who have progressed on at least 1 line of endocrine therapy. Unlike other oral selective estrogen receptor degraders (SERDs), vepdegestrant recruits an E3 ubiquitin ligase to degrade the ER through the ubiquitination and proteasome system and is released after degradation to initiate subsequent cycles of receptor destruction. Like other oral SERDs, its regulatory path is currently restricted to patients with ESR1 mutations, which is a primary resistance mechanism following aromatase inhibitor therapy, and McCann emphasized that combination therapy trials will be critical to expanding its utility. She cited the phase 1b/2 ELEVATE trial (NCT05563220) examining elacestrant (Orserdu) with ribociclib (Kisqali) and abemaciclib (Verzenio). She concluded that treatment decisions will largely be driven by patient preference, with the long-term goal of replacing injectable therapies such as fulvestrant (Faslodex) with effective oral alternatives.
FDA Approval of Decitabine/Cedazuridine Plus Venetoclax in AML: Courtney DiNardo, MD, MSCE
Courtney D. DiNardo, MD, MSCE, of The University of Texas MD Anderson Cancer Center and The University of Texas Graduate School of Biomedical Sciences, details the significance of the FDA approval of decitabine and cedazuridine (Inqovi) combined with venetoclax (Venclexta) for use in adult patients with newly diagnosed acute myeloid leukemia (AML) who are at least 75 years of age or have comorbidities precluding intensive induction chemotherapy, supported by the phase 2 ASCERTAIN-V study (NCT04657081). At a median follow-up of 11.2 months, the regimen elicited a complete response (CR) rate of 46.5% (95% CI, 36.5%-56.7%), a CR with incomplete hematologic recovery rate of 63.4% (95% CI, 53.2%-72.7%), a median time to CR of 2.4 months, and a median overall survival (OS) of 15.5 months (95% CI, 7.6-not estimable). DiNardo noted that although the mechanism of action is similar to venetoclax paired with azacitidine (Vidaza) or decitabine, which was previously cleared in October 2020, the key distinction is that decitabine/cedazuridine plus venetoclax offers an entirely oral regimen. She concluded that this all-oral option is particularly meaningful for patients with AML, who tend to be older and have typically required extended hospital time for intravenous therapy.
FDA Approval of Adjuvant Atezolizumab in MRD+ MIBC: Jason Hafron, MD
Jason Hafron, MD, of the Michigan Institute and the William Beaumont School of Medicine at Oakland University, unpacks the FDA approval of atezolizumab (Tecentriq) and atezolizumab plus hyaluronidase-tqjs (Tecentriq Hybreza) as adjuvant treatment for adult patients with muscle-invasive bladder cancer (MIBC) after cystectomy who have circulating tumor DNA (ctDNA) molecular residual disease (MRD), as determined by an FDA-authorized test. The decision was supported by the phase 3 IMvigor011 trial (NCT04660344), in which adjuvant atezolizumab led to a median disease-free survival (DFS) of 9.9 months vs 4.8 months with placebo (HR, 0.64; 95% CI, 0.47-0.87; P = .0047) and a median OS of 32.8 months vs 21.1 months with placebo (HR, 0.59; 95% CI, 0.39-0.90; P = .0131). Hafron characterized IMvigor011 as the first trial to prospectively use a ctDNA biomarker in this setting, providing level one evidence that ctDNA-informed treatment can substantially improve outcomes, and describes ctDNA as a disruptive technology enabling more precise patient selection. He concluded that these data mark the beginning of a broader transition toward biomarker-driven strategies in bladder cancer management.
Clinical Trial Design Considerations in Multiple Myeloma: Rebecca Silbermann, MD, MMS
Rebecca Silbermann, MD, MMS, of the School of Medicine of Oregon Health & Science University, addresses key clinical trial design considerations in multiple myeloma—including supportive care measures, end point selection, and enrollment of underrepresented populations—as highlighted at the CoMMit Consortium during the 2025 ASH Annual Meeting and Exposition. She noted variability among centers in managing cytokine release syndrome for patients receiving talquetamab-tgvs (Talvey), with some using dexamethasone and others tocilizumab (Actemra), illustrating the need for pragmatic, resource-sensitive trial designs that can be implemented broadly across practice settings. Silbermann also highlighted encouraging French data on dexamethasone-sparing strategies in frail patients, reinforcing the need for trials to incorporate patient-centered end points where minimizing toxicity and preserving quality of life may take precedence over achieving minimal residual disease negativity. She concluded that emerging information on erythrocyte Duffy genotype and racial disparities in treatment response underscore substantial knowledge gaps, and that future trial designs must address biologic and sociodemographic disparities to improve equity in myeloma outcomes.
Timing of Delayed or Re-Emergent irAEs in Melanoma: Michael A. Postow, MD
Michael A. Postow, MD, of Memorial Sloan Kettering Cancer Center, explores the distinct and evolving toxicity profile of immune checkpoint inhibitors (ICIs) in melanoma, underscoring that, unlike traditional therapies, ICI-mediated immune modulation can alter immune function in prolonged and sometimes permanent ways. Immune-related adverse effects (irAEs) vary widely in timing and presentation—delayed irAEs can emerge more than 1 year after treatment initiation, and chronic irAEs may persist beyond 3 years after the final dose. They can also affect multiple organ systems, including endocrine, dermatologic, gastrointestinal, pulmonary, and rheumatologic pathways. Postow emphasized the importance of maintaining a high index of suspicion when examining new or persistent symptoms in patients with prior exposure to immunotherapy, as the oncology community is still in the early stages of understanding these long-term mechanisms. He concluded that shared responsibility among oncologists, multidisciplinary care teams, and patients is essential for monitoring late-emerging toxicities and that continued research is needed to optimize recognition and long-term management of chronic irAEs.
