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:
Teclistamab Plus Daratumumab vs Daratumumab-Based Triplets in R/R Multiple Myeloma: Luciano J. Costa, MD, PhD
Luciano Costa, MD, of The University of Alabama at Birmingham (UAB) School of Medicine and the UAB O’Neal Comprehensive Cancer Center, unpacked the clinical relevance of data from the phase 3 MajesTEC-3 trial (NCT05083169) shared during the 2025 ASH Annual Meeting. Data indicated that teclistamab-cqyv (Tecvayli) plus daratumumab (Darzalex) significantly improved progression-free survival (PFS) vs established daratumumab-based regimens in patients with relapsed or refractory multiple myeloma who had previously received 1 to 3 lines of therapy. Costa noted that the magnitude of benefit was unexpected and that an overall survival (OS) advantage favoring the teclistamab-based regimen was observed at the first interim analysis. He underscored that these data support a growing role for T-cell–engaging therapies earlier in treatment, while underscoring the importance of shared decision-making when weighing bispecific antibodies against CAR T-cell therapy.
Potential Role of TROP2-Directed ADCs in IO-Ineligible TNBC: Kevin Kalinsky, MD, MS
Kevin Kalinsky, MD, MS, FASCO, of Emory University School of Medicine and Winship Cancer Institute, discussed the evolving role of TROP2-directed antibody-drug conjugates (ADCs) in metastatic triple-negative breast cancer. He explained that findings from phase 3 trials such as ASCENT-04 (NCT05382286), ASCENT-03 (NCT04827927), and TROPION-Breast02 (NCT04484142) support these agents as potential frontline standards, irrespective of PD-L1 status. Sacituzumab govitecan-hziy (Trodelvy) and datopotamab deruxtecan-dlnk (Datroway) both showcased significant improvements in PFS vs chemotherapy, with differing schedules and safety profiles. Kalinsky emphasized that although having 2 effective TROP2-directed options is beneficial, there are currently no data to guide sequencing one ADC after another.
Evolving Role of SERDs/Targeted Therapies in Advanced HR+ Breast Cancer: Hope S. Rugo, MD
Hope S. Rugo, MD, of City of Hope, explained how targeted therapies and novel oral selective estrogen receptor degraders are reshaping treatment for advanced hormone receptor–positive breast cancer. She highlighted data from the phase 2/3 INAVO120 trial (NCT04191499), in which inavolisib (Itovebi) plus palbociclib (Ibrance) and fulvestrant (Faslodex) improved PFS and OS in patients with PIK3CA-mutated disease. Rugo also reviewed findings from the phase 3 evERA Breast Cancer trial (NCT05306340), which examined giredestrant plus everolimus (Afinitor), noting particular benefit in ESR1-mutant tumors and improved response rates overall. She underscored that careful toxicity management, including hyperglycemia and stomatitis, is essential to safely extend the duration of effective oral therapy.
FDA Approval of Frontline T-DXd Plus Pertuzumab For Metastatic HER2+ Breast Cancer: Sara M. Tolaney, MD, MPH
Sara M. Tolaney, MD, MPH, of Dana-Farber Cancer Institute, discussed the FDA approval of fam-trastuzumab deruxtecan-nxki (Enhertu) plus pertuzumab (Perjeta) for frontline treatment in patients with unresectable or metastatic HER2-positive breast cancer. The decision was supported by findings from the phase 3 DESTINY-Breast09 trial (NCT04784715), which demonstrated a significant improvement in PFS vs trastuzumab (Herceptin), pertuzumab, and taxane (THP). At the time of the interim analysis, the median PFS improved from 26.9 months (95% CI, 21.8-not estimable [NE]) with THP to 40.7 months (95% CI, 36.5-NE) with the T-DXd–based regimen, corresponding to a hazard ratio of 0.56 (95% CI, 0.44-0.71; P < .0001). Although OS data were immature, Tolaney noted that the magnitude and durability of PFS benefit strongly support this regimen in the frontline setting.
Rationale for Investigating Telisotuzumab Adizutecan in ctDNA+ CRC: Kanwal Raghav, MBBS, MD
Kanwal P.S. Raghav, MBBS, MD, of The University of Texas MD Anderson Cancer Center, discussed the rationale for targeting minimal residual disease in colorectal cancer (CRC) using circulating tumor DNA (ctDNA)–guided therapy. He explained that ctDNA positivity following adjuvant treatment is a strong predictor of recurrence and may represent a window for curative intervention. This strategy is being examined in a phase 2 trial (NCT07023289) of telisotuzumab adizutecan (ABBV-400; Temab-A), a MET-directed ADC, in patients with ctDNA-positive CRC. Raghav emphasized that the study aims to determine whether early intervention with Temab-A can improve disease-free survival and potentially alter the natural history of high-risk disease.
