Five Under 5: Top Oncology Videos for the Week of 11/16

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:

Rationale for Targeting NaPi2b in Ovarian Cancer: Antonio Gonzalez-Martin, MD

Antonio Gonzalez-Martin, MD, of Clinica Universidad de Navarra and Cancer Center Clinica Universidad de Navarra, discusses the rationale for targeting NaPi2b in ovarian cancer and the development of the antibody-drug conjugate (ADC) TUB-040. He explained that patients with platinum-resistant ovarian cancer face a major unmet need, making ADCs a key area of investigation. Gonzalez-Martin described TUB-040 as an exatecan-based ADC with a stable linker that targets NaPi2b, a highly expressed transporter protein on ovarian cancer cells, making it an appealing therapeutic target in this paradigm. He spotlighted the phase 1/2a NAPISTAR1-01 trial (NCT06303505), which examined TUB-040 in patients with heavily pretreated, platinum-resistant high-grade serous ovarian cancer and assessed safety, tolerability, and preliminary efficacy.

Clinical Presentation and Management of LEMS in SCLC: Erminia Massarelli, MD, PhD, MS

Erminia Massarelli, MD, PhD, MS, of UT Health East Texas HOPE Cancer Center, discusses the importance of early recognition and management of Lambert–Eaton myasthenic syndrome (LEMS) in patients with small cell lung cancer (SCLC). She explained that LEMS, a paraneoplastic neuromuscular disorder marked by proximal lower-extremity weakness and diminished reflexes, must be distinguished from myasthenia gravis to ensure accurate diagnosis and that the right therapy is administered. Massarelli emphasized that amifampridine is the central symptomatic treatment for LEMS as it boosts function by strengthening presynaptic acetylcholine release. She added that although LEMS occurs in a minority of patients with SCLC, it may be linked with prolonged survival, underscoring the need for oncologists to identify and treat it promptly.

Management Challenges in STK11/KEAP1+, SMARCA4-Deficient Undifferentiated Tumors and NUT Carcinoma: Benjamin Herzberg, MD

Benjamin Herzberg, MD, of Herbert Irving Comprehensive Cancer Center, discusses the clinical challenges faced with several aggressive lung cancer subsets, including STK11/KEAP1-mutated tumors, SMARCA4-deficient undifferentiated tumors, and NUT carcinoma. He explained that STK11/KEAP1 and SMARCA4 mutations, particularly when co-occurring with KRAS, are associated with poor prognosis and limited response to chemotherapy, immunotherapy, and radiation, prompting significant concern when these patterns appear. He noted that NUT carcinoma should be suspected in poorly differentiated tumors that do not have clear lineage markers, as it progresses fast, and NUTM1 rearrangements must be identified to inform referral to investigational therapies. Herzberg added that SMARCA4-deficient tumors demonstrate highly aggressive biology and have no established standard of care; patients with these tumors achieve variable responses to immunotherapy. He emphasized that early molecular profiling, diagnostic vigilance, and timely referral to clinical trials are critical for patients with these high-risk tumor subsets.

Efficacy Findings With ctDNA-Guided Adjuvant Atezolizumab in MIBC: Joaquim Bellmunt, MD, PhD

Joaquim Bellmunt, MD, PhD, of Dana-Farber Cancer Institute and Harvard Medical School, discusses results from the phase 3 IMvigor011 trial (NCT04660344) examining circulating tumor DNA (ctDNA)–guided adjuvant atezolizumab (Tecentriq) in patients with muscle-invasive bladder cancer. He reported that ctDNA-positive patients who received atezolizumab experienced significantly longer disease-free survival (DFS) vs those given a placebo, with a hazard ratio of 0.64; meaningful improvements in 12- and 24-month DFS rates were also achieved with atezolizumab. Bellmunt added that adjuvant atezolizumab also improved overall survival (OS) with a 41% reduction in risk of death vs placebo, and that this was the first OS benefit ever demonstrated with an adjuvant immunotherapy in this setting. He noted that ctDNA status may help determine which patients benefit from adjuvant treatment and could potentially spare others from unnecessary therapy.

Rationale Behind the EMBARK Trial in Prostate Cancer: Stephen J. Freedland, MD

Stephen Freedland, MD, of Cedars-Sinai Cancer Institute, spotlights the phase 3 EMBARK trial (NCT02319837) assessing enzalutamide (Xtandi) plus leuprolide in patients with high-risk, nonmetastatic prostate cancer that is progressing after radical prostatectomy, radiotherapy, or both. He noted that the addition of enzalutamide to androgen deprivation therapy significantly improves survival, delays disease progression, and has an acceptable safety profile, prompting the evaluation of its use earlier in the biochemical-recurrent, imaging-negative setting. Freedland highlighted that the trial’s primary end point was metastasis-free survival per blinded independent central review assessment. In the experimental arm, patients received enzalutamide 160 mg daily plus leuprolide every 12 weeks.