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:
Importance of Biomarker Testing in Head and Neck Cancers: Fangdi Sun, MD
Fangdi Sun, MD, of Stanford University, discusses the critical role of biomarkers in navigating the diverse malignancies that comprise the head and neck cancer umbrella, emphasizing that biomarker identification is no longer optional but necessary for diagnosis and treatment decision-making. In advanced salivary gland malignancies, next-generation sequencing (NGS) is both diagnostically and therapeutically useful, revealing characteristic molecular findings such as MYB fusions in adenoid cystic carcinoma or NTRK fusions in secretory carcinoma, as well as targetable vulnerabilities like androgen receptor or HER2 expression commonly found in salivary ductal carcinomas. For head and neck squamous cell carcinoma, Sun stressed mandatory biomarker testing, particularly human papillomavirus (HPV) status via p16 immunohistochemistry or high-risk HPV in situ hybridization for oropharyngeal primaries, and Epstein-Barr virus via Epstein-Barr encoding region in situ hybridization for nasopharyngeal cancers, given that these distinctions carry significant prognostic and therapeutic implications. She concluded that in cases of squamous cell carcinoma isolated to a lymph node, NGS or tumor mutational burden can identify ultraviolet-induced damage signatures to distinguish cutaneous from mucosal primary sites, and that a deep molecular understanding of disease is the only way to provide effective care.
Current Landscape of Biomarker-Driven Approaches in Esophageal Cancer: Peter C. Enzinger, MD
Peter C. Enzinger, MD, of Dana-Farber Cancer Institute and Harvard Medical School, discusses currently available and emerging biomarker-driven therapeutic strategies in esophageal cancer, with particular focus on HER2 and Claudin 18.2 (CLDN18.2) as key targets. The October 2024 FDA approval of zolbetuximab (Vyloy) plus platinum- and fluoropyrimidine-containing chemotherapy for patients with untreated, locally advanced or metastatic, HER2-negative, CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma was supported by findings from the phase 3 SPOTLIGHT trial (NCT03504397) examining zolbetuximab with mFOLFOX6 and data from the phase 3 GLOW trial (NCT03653507) assessing the agent with CAPOX. The decision represents a significant shift for patients with HER2-negative disease. Although HER2-targeted agents like trastuzumab (Herceptin) and fam-trastuzumab deruxtecan-nxki (Enhertu) have been vital for over a decade, Enzinger asserted that the future of gastroesophageal therapy lies in refining these existing targets and exploring emerging ones like FGFR, MET, EGFR, EpCAM, and C-CAM. He concluded that the overarching goal for the field is to expand biomarker-driven therapies as quickly and broadly as possible to improve outcomes for patients with this disease.
Role of ctDNA-Guided Therapy in RCC: Taigo Kato, MD, PhD
Taigo Kato, MD, PhD, of Osaka University Graduate School of Medicine, discusses the present role of circulating tumor DNA (ctDNA)–guided therapy in renal cell carcinoma (RCC) and the utility of the whole genome sequencing (WGS) panel examined in the prospective MONSTAR-SCREEN-3 study (UMIN000053975). Drawing on findings from the phase 3 IMvigor011 trial (NCT04660344), which demonstrated that ctDNA status can inform adjuvant therapy decisions in muscle-invasive bladder cancer, Kato explained that a similar approach in RCC could reduce disease recurrence risk by identifying which patients are appropriate candidates for adjuvant therapy. The personalized ctDNA panel leveraged in MONSTAR-SCREEN-3 was tailored to each patient and contained 1,000 somatic values derived from whole exome sequencing data, which while not yet common in daily practice has proven to be a useful and informative strategy. Kato concluded that as the cost of WGS continues to decline, it may soon be applied in a manner comparable to whole exome sequencing, further expanding ctDNA-guided precision oncology in this disease.
Use of CDK4/6 Inhibitors Plus Endocrine Therapy in Breast Cancer: Rena D. Callahan, MD
Rena D. Callahan, MD, of UCLA Health and the David Geffen School of Medicine at UCLA, explains the clinical confidence provided by 4-year data from the phase 3 NATALEE trial (NCT03701334) examining adjuvant ribociclib (Kisqali) in combination with endocrine therapy in patients with hormone receptor–positive, HER2-negative early breast cancer. Consistent with data from the phase 3 monarchE trial (NCT03155997) examining abemaciclib (Verzenio), NATALEE showed that adding a CDK4/6 inhibitor to endocrine therapy in patients with high-risk early-stage hormone receptor–positive breast cancer leads to a substantial and growing difference in relapse rates over time. Callahan highlighted that the statistical separation between outcomes in patients receiving endocrine therapy alone vs in combination with a CDK4/6 inhibitor widens with longer follow-up, and since ribociclib is prescribed for 3 years in NATALEE, establishing efficacy beyond that time point was critical to confirm a durable benefit that persists following treatment completion. She further noted that NATALEE's inclusion of patients with node-negative breast cancer significantly expands the potential treatment population who may benefit from this regimen.
Mechanism of Action of Darlifarnib in ccRCC: Adanma Ayanambakkam, MD, MS
Adanma Ayanambakkam, MD, MS, of the Stephenson Cancer Center at the University of Oklahoma Health Sciences Center, discusses the mechanism of action of darlifarnib (KO-2806) for use in patients with clear cell RCC. Darlifarnib is a next-generation farnesyltransferase inhibitor that blocks farnesylation to prevent mTOR1 activation, distinguishing itself from other mTOR inhibitors like everolimus (Afinitor) through its high specificity for mTOR1, which could confer a better safety and tolerability profile. Darlifarnib paired with cabozantinib (Cabometyx) was examined in the first-in-human phase 1a/1b FIT-001 trial (NCT06026410) in adult patients with advanced solid tumors, requiring at least 1 prior immunotherapy-based regimen and a Karnofsky performance score of at least 70 for those with clear cell RCC. Preliminary findings from FIT-001 were shared at the 2026 International Kidney Cancer Symposium: Europe.
