Five Under 5: Top Oncology Videos for the Week of 8/24

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:

Persisting Knowledge Gaps Surrounding the Use of ADCs in Lung Cancer: Jyoti Malhotra, MD, MPH

Jyoti Malhotra, MD, MPH, of City of Hope, discusses the efficacy of antibody-drug conjugates (ADCs) in patients with non–small cell lung cancer (NSCLC) and brain metastases. Several ADCs use camptothecin as their payload, a compound already recognized for activity in the brain. Although clinical trials have demonstrated encouraging signs of central nervous system (CNS) efficacy, the mechanism by which ADCs act on brain tumors is not well understood. This knowledge gap underscores the need for further research to define their role and optimize treatment strategies. She added that a key unanswered question is which patients can safely delay radiation when treated with an ADC. Ongoing studies may provide critical insight into this area.

Clinical Applicability of Cyclin E1 Protein Expression as a Biomarker for Response to Azenosertib in Ovarian Cancer: Fiona Simpkins, MD

Fiona Simpkins, MD, of the University of Pennsylvania Perelman School of Medicine, discusses the role of cyclin E1 protein expression as a biomarker of response to azenosertib (ZN-c3) in ovarian cancer. Data from part 1b of the phase 2 DENALI trial (NCT05128825) demonstrated that cyclin E1 expression is present in about half of platinum-resistant ovarian cancers, expanding the potential population for WEE1 inhibition beyond CCNE1 gene amplification. In this heavily pretreated setting, azenosertib elicited an objective response rate of 34.9% with a median response duration of 6.3 months, findings Simpkins called encouraging given historically poor outcomes. She noted that ongoing analyses aim to validate cyclin E1 as a predictive biomarker and refine patient selection. These data support continued development of azenosertib and biomarker-driven approaches to improve outcomes in platinum-resistant ovarian cancer.

Current Role of Sentinel Node Biopsies in Breast Cancer: Deba Sarma, MD

Deba Sarma, MD, of the Atrium Health Levine Cancer Institute and Wake Forest University School of Medicine, discusses the role of sentinel node biopsies in breast cancer. She explained that invasive ductal and lobular carcinomas often spread to the axillary lymph nodes, with imaging such as ultrasound or mammogram guiding the diagnostic workup. At surgery, whether lumpectomy or mastectomy, the standard is removal of the first 2 to 3 lymph nodes, although this carries risks such as pain, nerve or vascular injury, decreased range of motion, and lymphedema. She emphasized that the necessity of sentinel node biopsies for all patients remains under question. Future research must clarify whether omission is safe without compromising outcomes or influencing management decisions across oncology disciplines.

Rationale for Evaluating Darolutamide Plus ADT in High-Risk Biochemical Recurrence of Prostate Cancer: Alicia Morgans, MD, MPH

Alicia Morgans, MD, MPH, of Harvard Medical School and Dana-Farber Cancer Institute, discusses the rationale for examining darolutamide (Nubeqa) combined with androgen deprivation therapy (ADT) in patients with high-risk biochemical recurrence of prostate cancer. The phase 3 ARISTEP trial (NCT05794906) enrolled patients with prostate-specific membrane antigen (PSMA) PET–positive metastatic disease after surgery or radiation, who were randomized to receive ADT alone or ADT plus darolutamide for 2 years. Metastasis-directed radiation was optional. Morgans noted that androgen receptor pathway inhibitors have already shown benefit across metastatic and nonmetastatic settings, including enzalutamide (Xtandi) in the phase 3 EMBARK trial (NCT02319837). The study’s goal is to determine whether darolutamide plus ADT can prolong the time to PSMA PET progression, a potential paradigm-shifting end point in this setting. She added that this approach could provide insight into how PSMA PET progression correlates with other outcomes, such as metastasis-free survival.

Management of ADC-Related Toxicities in Breast Cancer: Antoinette Tan, MD, MHS

Antoinette Tan, MD, MHS, of Atrium Health Levine Cancer and Wake Forest University School of Medicine, discusses the safety profile of ADCs for the treatment of patients with breast cancer. She explained that although ADCs generally cause less toxicity than standard chemotherapy, proactive management remains essential to avoid dose-limiting adverse effects. Dose reductions can often help mitigate ADC-related toxicities, she noted. Tan highlighted that ADCs vary in their targets and payloads, which can influence their toxicity profiles. For example, trastuzumab govitecan-hziy (Trodelvy) is associated with mild marrow suppression and gastrointestinal toxicities, whereas fam-trastuzumab deruxtecan-nxki (Enhertu) carries a risk of interstitial lung disease. She emphasized the importance of considering patients’ underlying conditions when selecting an ADC, particularly given the limited prospective data on recently approved agents.