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:
Kidney Cancer Abstracts to Watch at ASCO GU 2026: Jad Chahoud, MD, MPH, MHA
Jad Chahoud, MD, MPH, of Orlando Health Cancer Institute, discusses kidney cancer trials poised to influence clinical practice at the 2026 ASCO Genitourinary Cancers Symposium. He highlighted the phase 3 LITESPARK-022 trial (NCT05239728), which is examining adjuvant pembrolizumab (Keytruda) plus belzutifan (Welireg) vs pembrolizumab plus placebo in high-risk clear cell renal cell carcinoma. Chahoud noted that although adjuvant pembrolizumab has showcased benefit, relapse risk remains significant, making combination strategies clinically compelling. He also discussed the phase 3 LITESPARK-011 trial (NCT04586231), which is comparing lenvatinib (Lenvima) plus belzutifan with cabozantinib (Cabometyx) following previous PD-(L)1 therapy, emphasizing that progression-free survival magnitude and patient-reported outcomes will be key to defining practice impact.
CALR-Directed Agents and Investigational Targeted Therapies in MPNs: John O. Mascarenhas, MD
John O. Mascarenhas, MD, of the Icahn School of Medicine at Mount Sinai and The Tisch Cancer Institute, discusses the shift toward molecularly driven therapies in myeloproliferative neoplasms (MPN). He reviewed early-phase data from the INCA033989-101 (NCT05936359) and INCA033989-102 (NCT06034002) trials examining the CALR-targeted monoclonal antibody INCA033989 in CALR exon 9–mutated myelofibrosis. Mascarenhas reported that the agent had favorable tolerability both as single agent and in combination with ruxolitinib (Jakafi); no dose-limiting toxicities were observed. He explained that promising spleen volume reductions and on-target activity support further development of CALR-directed strategies to move MPN care beyond a one-size-fits-all JAK inhibitor approach.
HER2-Directed Treatment Sequencing in Breast Cancer Brain Metastases: Vikram C. Gorantla, MD
Vikram C. Gorantla, MD, of the University of Pittsburgh Medical Center Hillman Cancer Center, discusses evolving treatment sequencing for HER2-positive metastatic breast cancer with brain metastases. He focused on real-world outcomes comparing fam-trastuzumab deruxtecan-nxki (Enhertu) with a tucatinib (Tukysa), trastuzumab (Herceptin), and capecitabine (Xeloda) regimen in the second-line setting. Gorantla reported that trastuzumab deruxtecan was linked with a longer real-world time to next treatment and a reduced likelihood of requiring subsequent therapy. He raised ongoing concerns about disease biology following progression on the antibody-drug conjugate, questioning whether HER2 expression changes or clonal selection may influence outcomes with later-line therapies.
Continued Investigation of Elenestinib in Indolent Systemic Mastocytosis: Deepti Radia, MBBS, BSc, MRCPI, FRCPath, MSc Med Ed
Deepti Radia, MBBS, BSc, MRCPI, FRCPath, MSc Med Ed, of Guy’s and St Thomas’ NHS Foundation Trust, discusses data from part 1 of the phase 2/3 HARBOR trial (NCT04910685) examining elenestinib (BLU-263) in indolent systemic mastocytosis. She explained that dose-finding results identified elenestinib 75 mg once daily as the optimal dose to advance based on safety and biomarker improvements. Radia noted that elenestinib was well tolerated spanning assessed dose levels and showcased activity against KIT D816V–driven disease. She outlined that part 2 will further examine efficacy in a larger randomized population, including cohorts previously treated with KIT D816V inhibitors.
Integration of NALIRIFOX Into the Frontline Metastatic Pancreatic Cancer Paradigm: Shubham Pant, MD, MBBS
Shubham Pant, MD, MBBS, of The University of Texas MD Anderson Cancer Center, discusses the role of NALIRIFOX (irinotecan liposome [Onivyde], oxaliplatin, 5-fluorouracil, and leucovorin) in the frontline treatment of patients with metastatic pancreatic cancer. He reviewed findings from the phase 3 NAPOLI 3 trial (NCT04083235), which supported the FDA approval of NALIRIFOX after showcasing improved OS compared with gemcitabine plus nab-paclitaxel (Abraxane). Pant highlighted that the regimen offers a distinct safety profile, including lower rates of neuropathy because of reduced-dose oxaliplatin. He underscored careful patient selection and monitoring for gastrointestinal toxicities, concluding that NALIRIFOX is an effective frontline option for many patients.
