Five Under 5: Top Oncology Videos for the Week of 10/12

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:

Potential Role of CELMoDs in Multiple Myeloma Management: Jesús Berdeja, MD

Jesús Berdeja, MD, of Sarah Cannon Research Institute and Tennessee Oncology, examined how cereblon E3 ligase modulators (CELMoDs), which bind cereblon more potently and activate the immune system more strongly than immunomodulatory drugs, could reshape multiple myeloma management. In August 2026, the FDA granted accelerated approval to iberdomide (Zenbexus) plus daratumumab and hyaluronidase-fihj (Darzalex Faspro) and dexamethasone for patients with relapsed/refractory multiple myeloma who received at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent. The approval was based on the phase 3 EXCALIBER-RRMM trial (NCT04975997), in which the minimal residual disease–negative complete response rate was 41% with the iberdomide regimen (n = 207) vs 21% with daratumumab, bortezomib (Velcade), and dexamethasone (P < .0001). In the phase 3 SUCCESSOR-2 trial (NCT05552976), mezigdomide plus carfilzomib (Kyprolis) and dexamethasone produced a median progression-free survival (PFS) of 18.0 months vs 8.3 months with carfilzomib and dexamethasone alone among patients previously treated with lenalidomide (Revlimid) and an anti-CD38 antibody (HR, 0.48; 95% CI, 0.36-0.63; P < .001). Berdeja noted that CELMoD-based combinations have outperformed standard-of-care regimens in prospective studies and could replace some current options.

Development of Novel Approaches in Endocrine-Resistant Hormone Receptor–Positive Breast Cancer: Matthew Goetz, MD

Matthew Goetz, MD, of Mayo Clinic Comprehensive Cancer Center, outlined emerging strategies for endocrine-resistant hormone receptor–positive, HER2-negative breast cancer, distinguishing this population from patients with endocrine-sensitive disease who often respond well to a CDK4/6 inhibitor plus endocrine therapy. He described gedatolisib (Revtorpyk), an intravenous inhibitor of all class I PI3K isoforms and mTORC1/mTORC2, which the FDA approved in July 2026 with fulvestrant (Faslodex), with or without palbociclib (Ibrance), for patients without a PIK3CA mutation whose disease progressed on endocrine therapy in the metastatic setting. Goetz noted that optimal sequencing after CDK4/6 inhibitor resistance remains unresolved, including whether gedatolisib should precede or follow investigational oral allosteric PI3K inhibitors. For tumors harboring both ESR1 and PIK3CA mutations, he favored studying combined targeting, such as imlunestrant (Inluriyo) plus a PI3K-directed agent, over sequential therapy. He added that because antibody-drug conjugates are essentially chemotherapy, developing targeted endocrine-based approaches that delay chemotherapy is a key priority over the next 10 to 15 years.

Integration of CAR T-Cell Therapy Into Earlier Myeloma Treatment Lines: Doris Hansen, MD

Doris Hansen, MD, of Moffitt Cancer Center, reviewed the rationale for moving chimeric antigen receptor (CAR) T-cell therapy into earlier lines of multiple myeloma treatment. The phase 1b/2 CARTITUDE-1 trial (NCT03548207) supported the February 2022 FDA approval of ciltacabtagene autoleucel (cilta-cel; Carvykti) for patients with at least 4 prior lines of therapy, and Hansen noted that approximately one-third of treated patients achieved a functional cure. In cohort A of the phase 2 CARTITUDE-2 trial (NCT04133636), which enrolled patients with 1 to 3 prior lines, the 5-year PFS rate was 54.2% (95% CI, 30.3%-73.0%) and the 5-year overall survival rate was 69.2% (95% CI, 43.8%-84.9%) at a median follow-up of 60.7 months. Hansen said earlier use of CAR T-cell products, including cilta-cel and idecabtagene vicleucel (Abecma), yields better outcomes, and that patients with standard-risk disease may benefit as much as those with high-risk disease. She added that faster manufacturing, more effective bridging therapy, and the FDA's removal of Risk Evaluation and Mitigation Strategy requirements—which shortened the required stay near the treatment center from 4 weeks to 2 weeks—are easing access barriers.

Real-World Atrial Fibrillation and Cardiovascular Outcomes in CLL: Michael G. Fradley, MD

Michael G. Fradley, MD, of Penn Medicine, detailed findings from a retrospective analysis of the Symphony Health open claims database, presented at the 2026 ASCO Annual Meeting, that evaluated atrial fibrillation (AFib) and cardiovascular outcomes in chronic lymphocytic leukemia/small lymphocytic lymphoma. Among 233,362 patients with newly diagnosed disease, 13.1% developed AFib within 1 year of diagnosis. Compared with those who did not develop AFib, patients who did had higher rates of stroke (14.3% vs 8.9%), bleeding (27.9% vs 19.1%), and heart failure (54.5% vs 18.9%; all P < .0001). In an exploratory analysis of 22,636 patients initiating frontline BTK inhibitor therapy, AFib occurred in 16.0% of patients receiving ibrutinib (Imbruvica), 13.0% receiving acalabrutinib (Calquence), and 11.0% receiving zanubrutinib (Brukinsa; P < .0001), findings Fradley characterized as hypothesis-generating. Among patients with AFib, stroke occurred in 4.8% of those treated with zanubrutinib vs 12.2% of those treated with ibrutinib.

Navigation of Oral SERDs and Targeted Therapy in Advanced Breast Cancer: Matthew Goetz, MD

Matthew Goetz, MD, of Mayo Clinic Comprehensive Cancer Center, explored the evolving role of oral selective estrogen receptor degraders and targeted agents in hormone receptor–positive, HER2-negative advanced breast cancer. In the up-front setting, the phase 3 persevERA Breast Cancer (NCT04546009) and SERENA-4 (NCT04711252) trials did not meet their PFS end points when giredestrant or camizestrant (Etcamah), respectively, replaced an aromatase inhibitor alongside palbociclib, although Goetz noted that tolerability and quality-of-life differences may still matter. For PIK3CA-mutated disease, he pointed to the 2024 FDA approval of inavolisib (Itovebi) plus palbociclib and fulvestrant based on the phase 3 INAVO120 trial (NCT04191499), while questioning how the regimen compares with other PI3K-, AKT-, or mTOR-directed options. He added that investigational allosteric PI3K inhibitors may reduce adverse effects such as the hyperglycemia seen with alpelisib (Piqray). Goetz also described next-generation agents, including the selective CDK4 inhibitor atirmociclib (PF-07220060) and the CDK4/6 degrader BTX-9341, noting that ongoing trials will determine whether they overcome resistance.