Five Under 5: Top Oncology Videos for the Week of 6/8

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:

Significance of the FDA Approval of Taletrectinib for ROS1+ NSCLC: Nathan A. Pennell, MD, PhD

Nathan A. Pennell, MD, PhD, of Cleveland Clinic’s Taussig Cancer Institute, discusses the FDA approval of taletrectinib (Ibtrozi) for patients with ROS1-positive non–small cell lung cancer (NSCLC). The approval, granted on June 11, 2025, was supported by data from the phase 2 TRUST-I (NCT04395677) and TRUST-II (NCT04919811) trials, which showed high overall response rates (ORRs) and durable responses in both treatment-naive and previously treated patients. Pennell explains that ROS1-positive NSCLC, although rare, remains a key oncogene-driven subtype, and prior ROS1-targeted therapies have been limited by resistance and toxicity. He notes that taletrectinib may represent a best-in-class option due to its favorable efficacy and safety profile across diverse patient populations.

Efficacy and Safety of Obrixtamig With Topotecan in Advanced SCLC: Martin Wermke, MD

Martin Wermke, MD, of the National Center for Tumor Diseases Dresden, discusses the potential synergy between obrixtamig and topotecan in advanced small cell lung cancer (SCLC) based on early data from the phase 1 DAREON-9 trial (NCT05990738). In patients previously treated with platinum-based therapy, the combination yielded an ORR of 70% (95% CI, 47%-87%), with durable responses confirmed in 69% (95% CI, 39%-91%) of evaluable patients. Wermke emphasizes that although preliminary, these results suggest a benefit beyond what either agent provides alone and warrant further investigation. The safety profile aligned with known toxicities, including manageable cytokine release syndrome with obrixtamig and hematologic adverse effects (AEs) typical of topotecan.

QOL Data From SERENA-6 in ER+/HER2– Advanced Breast Cancer: Hope S. Rugo, MD

Hope S. Rugo, MD, of City of Hope, discusses quality-of-life (QOL) outcomes from the phase 3 SERENA-6 trial (NCT04964934) evaluating camizestrant plus a CDK4/6 inhibitor in patients with ER-positive, HER2-negative advanced breast cancer and an ESR1 mutation. At the 2025 ASCO Annual Meeting, data showed that patients treated with camizestrant experienced a median time to deterioration of 23.0 months vs 6.4 months with an aromatase inhibitor plus CDK4/6 inhibitor (HR, 0.53; 95% CI, 0.33-0.82; nominal P < .001). Rugo highlighted that QOL, as assessed by the EORTC QLQ-C30 questionnaire, was significantly better with camizestrant despite similar progression-free survival in both arms. Although camizestrant and this treatment strategy are not yet FDA approved, Rugo anticipates a regulatory decision within the year.

Dato-DXd Plus Rilvegostomig in Advanced/Metastatic NSCLC: Martin E. Gutierrez, MD

Martin E. Gutierrez, MD, of Hackensack Meridian Health, discusses findings from cohort 5 of the phase 1b TROPION-Lung04 trial (NCT04526691), which is evaluating datopotamab deruxtecan (Dato-DXd) plus rilvegostomig in the first-line treatment of advanced or metastatic NSCLC. Among 40 patients enrolled, the confirmed ORR was 57.5%, with a disease control rate of 95.0% and a median duration of response of 5.8 months. Gutierrez notes that responses were more pronounced in patients with nonsquamous histology and that 20 patients remain on treatment. Importantly, the combination showed a manageable safety profile, with key AEs such as interstitial lung disease and corneal abnormalities consistent with known toxicities. These data support the potential of Dato-DXd plus rilvegostomig as a chemotherapy-free treatment strategy in biomarker-unselected patients with NSCLC.

Importance of Biomarker Testing in HR+/HER2-Negative Advanced Breast Cancer: Kevin Kalinsky, MD, MS

Kevin Kalinsky, MD, MS, FASCO, of Emory University, discusses the critical role of biomarker testing in hormone receptor–positive, HER2-negative advanced breast cancer. He emphasizes the need to evaluate for ESR1 mutations, which often arise after aromatase inhibitor treatment and can guide the use of targeted therapies like elacestrant (Orserdu). Kalinsky also noted the therapeutic relevance of alterations in the PI3K/AKT/PTEN pathway and highlighted favorable safety data for capivasertib (Truqap) in this setting. He pointed to results from the phase 3 INAVO120 trial (NCT04191499), which showed an overall survival benefit with inavolisib (Itovebi) plus palbociclib (Ibrance) and fulvestrant (Faslodex) in patients with PIK3CA-mutant, endocrine-resistant disease. Lastly, Kalinsky stressed the importance of BRCA1/2 and PALB2 mutation testing, given the potential utility of PARP inhibitors beyond patients with germline mutations.