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:
Optimal Referral Timing for CAR T-Cell Therapy in Multiple Myeloma: Jesús Berdeja, MD
Jesús Berdeja, MD, of Sarah Cannon Research Institute and Tennessee Oncology, discusses CAR T-cell therapy referral approaches and optimal timing for patients with multiple myeloma. He noted that two BCMA-directed CAR T-cell therapies are currently FDA-approved: ciltacabtagene autoleucel (cilta-cel; Carvykti) and idecabtagene vicleucel (ide-cel; Abecma), for patients with relapsed/refractory multiple myeloma following at least 1 and at least 2 previous lines of therapy, respectively. With these options now available earlier in the treatment paradigm and the growing availability of other BCMA-directed options such as bispecific antibodies and antibody-drug conjugates, Berdeja emphasized that sequencing has become a clinically meaningful issue, and exposure to other BCMA-directed therapies before CAR T-cell therapy may compromise its efficacy. He stressed that thoughtful up-front planning is essential, and that for patients who are eligible for several BCMA-targeted strategies, CAR T-cell therapy should generally be prioritized first, given the risk of diminished response if pursued in later lines. Berdeja concluded that timely referral to specialized centers is critical, and community oncologists must proactively engage with these centers to identify appropriate candidates and optimize the timing of CAR T-cell therapy administration.
Future of HER2+ Breast Cancer Management: Sara M. Tolaney, MD, MPH
Sara M. Tolaney, MD, MPH, of Dana-Farber Cancer Institute and Harvard Medical School, discusses the rapid and transformative evolution of therapeutic approaches in the HER2-positive breast cancer paradigm across both metastatic and early-stage disease settings. Findings from the phase 3 DESTINY-Breast09 trial (NCT04784715) have established fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) plus pertuzumab (Perjeta) as a primary frontline treatment option for patients with HER2-positive metastatic breast cancer, and the phase 3 HER2CLIMB-05 trial (NCT05132582) has highlighted the importance of maintenance strategies with the triplet regimen of tucatinib (Tukysa), trastuzumab (Herceptin), and pertuzumab after taxane induction. In estrogen receptor–positive, HER2-positive advanced disease, the phase 3 PATINA trial (NCT02947685) evaluated the addition of the CDK4/6 inhibitor palbociclib (Ibrance) to endocrine therapy and HER2-targeted agents during maintenance therapy, further expanding the treatment toolkit. Tolaney concluded that although these developments have introduced a wealth of options for patients with metastatic disease, the current challenge lies in synthesizing these data to determine optimal therapy sequencing and selection to improve patient outcomes.
Efficacy With Daraxonrasib-Containing Regimens in First-Line Metastatic PDAC: Brian M. Wolpin, MD, MPH
Brian M. Wolpin, MD, MPH, of the Hale Family Center for Pancreatic Cancer Research, Dana-Farber Cancer Institute and Harvard Medical School, unpacks efficacy data with daraxonrasib (RMC-6236) as monotherapy or in combination with chemotherapy in patients with first-line metastatic pancreatic ductal adenocarcinoma (PDAC), presented from two phase 1/2 datasets (NCT06445062; NCT05379985) at the 2026 AACR Annual Meeting. In the GI-102 platform study, daraxonrasib plus gemcitabine and nab-paclitaxel (Abraxane) yielded an overall response rate (ORR) of 58% (95% CI, 41%-73%) in evaluable patients (n = 40); the disease control rate (DCR) was 90% (95% CI, 76%-97%), the 6-month progression-free survival (PFS) rate was 84% (95% CI, 68%-93%), and the 6-month overall survival (OS) rate was 90% (95% CI, 76%-96%). These outcomes were highly favorable compared with the 30% to 40% response rates and approximately 50% 6-month PFS rates typically observed with standard chemotherapy. When used as monotherapy in 38 efficacy-evaluable patients with RAS-mutant metastatic PDAC, daraxonrasib induced an ORR of 47% (95% CI, 31%-64%), a DCR of 92% (95% CI, 79%-98%), a 6-month PFS rate of 71% (95% CI, 53%-83%), and a 6-month OS rate of 83% (95% CI, 67%-92%). Wolpin concluded that although PFS and OS data remain immature and medians have not yet been reached, these early findings highlight the potential for RAS(ON) inhibitors to significantly improve outcomes for patients in the first-line setting.
Rationale for Comparing CRC Risk Reduction With GLP-1 Agonists vs Aspirin: Colton Jones, MD
Colton Jones, MD, of The University of Texas San Antonio, discusses the rationale for and results from a landmark head-to-head comparison of glucagon-like peptide-1 (GLP-1) receptor agonists vs aspirin for the primary prevention of colorectal cancer (CRC). This was prompted by data from the observational ASPREE study (NCT01038583), which demonstrated that aspirin provided no significant CRC risk reduction, increased the risk of major brain bleeding in older patients, and led the United States Preventive Services Task Force to remove its Category B recommendation for aspirin in CRC prevention. Using de-identified data from the TriNetX network representing approximately 150 million patients, the retrospective real-world analysis included 281,656 participants between the ages of 18 and 90 years, propensity-score matched into two equal cohorts of 140,828 patients receiving either GLP-1 receptor agonists or aspirin with a 6-month lead-in period. Data shared during the 2026 Gastrointestinal Cancers Symposium indicated that at a median follow-up of 6 years, GLP-1 receptor agonist use was linked with a 35.7% lower risk of CRC overall vs aspirin (HR, 0.643; 95% CI, 0.531-0.778), and a 42.1% lower risk in high-risk patients based on health or family history (HR, 0.579; 95% CI, 0.401-0.837). Jones concluded that this first-ever head-to-head comparison of these strategies revealed that GLP-1 receptor agonists offered superior efficacy and better tolerability than aspirin, suggesting they may represent a viable new pharmacologic standard for CRC prevention.
Frontline Standards of Care in Advanced or Metastatic Melanoma: Mario Sznol, MD
Mario Sznol, MD, of the Miller School of Medicine, Sylvester Comprehensive Cancer Center, University of Miami Health System, discusses the current first-line systemic treatment landscape for patients with advanced or metastatic melanoma, with a focus on dual immune checkpoint blockade approaches that continue to define the standard of care in the United States. Doublet immunotherapy combining CTLA-4 and PD-1 inhibition—most notably ipilimumab (Yervoy) plus nivolumab (Opdivo) and nivolumab plus relatlimab-rmbw (Opdualag)—has consistently shown improved PFS over single-agent therapy, with OS trends clearly favoring these combinations, solidifying dual immunotherapy as the preferred frontline option for appropriate candidates. Several ongoing phase 3 trials continue to assess novel combinations and sequencing strategies, including targeted agents and alternative immunotherapy backbones, although no regimen has yet shown superiority over established doublet combinations. Sznol concluded that although dual checkpoint inhibition remains the benchmark for frontline treatment, the higher rates of immune-related adverse effects linked with combination vs monotherapy necessitate careful patient selection based on performance status, comorbidities, and anticipated toxicity profiles.
