Five Under 5: Top Oncology Videos for the Week of 11/8

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:

Individualizing First-Line and Maintenance Strategies for HER2+ Metastatic Breast Cancer: Alison Conlin, MD

Alison Conlin, MD, of Providence Cancer Institute Franz Clinic, examined how first-line and maintenance treatment decisions can be individualized for patients with HER2-positive metastatic breast cancer. Conlin noted that the phase 3 DESTINY-Breast09 trial (NCT04784715) supported first-line fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) plus pertuzumab (Perjeta), and that an exploratory analysis favored this regimen in patients with baseline brain metastases. She added that newly diagnosed patients should undergo MRI to assess for central nervous system involvement, and that a HER2 TKI such as tucatinib (Tukysa) was likely the next best option after T-DXd. Drawing on the phase 3 PATINA (NCT02947685) and HER2CLIMB-05 (NCT05132582) trials, she said treating until progression or toxicity and an induction-maintenance approach were both reasonable in select patients. Conlin concluded that treatment goals and quality of life should guide selection, noting that a frail older patient might not be an ideal candidate for an aggressive upfront regimen.

How the EGFR-Targeted Therapy Landscape Has Evolved in NSCLC: Benjamin P. Levy, MD

Benjamin P. Levy, MD, of Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital, reviewed how frontline treatment for EGFR-mutated non–small cell lung cancer has evolved beyond single-agent osimertinib (Tagrisso). He explained that the phase 3 FLAURA2 trial (NCT04035486) added chemotherapy to osimertinib, which increased toxicity but involved adverse effects that oncologists were familiar with managing. Levy noted that amivantamab-vmjw (Rybrevant), a bispecific antibody targeting EGFR and MET, plus lazertinib (Lazcluze) in the phase 3 MARIPOSA trial (NCT04487080) produced an overall survival benefit of roughly 12 months, which he described as one of the largest seen in this population. Paronychia, rash, and diarrhea were key challenges with the combination, and proactive mitigation strategies were being evaluated in the phase 2 COCOON (NCT06120140) and SKIPPirr (NCT05663866) trials. Levy emphasized shared decision-making that weighed benefit against toxicity, treatment burden, and cost based on each patient's preferences.

BEHOLD-1 Data With Mocertatug Rezetecan in Platinum-Resistant Ovarian Cancer: Floor J. Backes, MD

Floor J. Backes, MD, of The Ohio State University Wexner Medical Center and the Ohio State University Comprehensive Cancer Center–James, highlighted updated data from the platinum-resistant ovarian cancer cohort of the phase 1 BEHOLD-1 trial (NCT06431594) with the B7-H4–directed antibody-drug conjugate mocertatug rezetecan, presented at the 2026 ESMO Congress. In the cohort (n = 136), confirmed objective response rates were 62%, 57%, and 36% at the 5.8-mg/kg, 4.8-mg/kg, and 2.8-mg/kg doses, respectively, with corresponding median progression-free survival (PFS) of 11.1, 8.3, and 5.6 months. Backes noted that high response rates did not always translate into PFS benefit, underscoring the need for confirmation in the phase 3 BEHOLD-Ovarian01 trial (NCT07286266), with Backes as principal investigator. Responses occurred across B7-H4 expression levels, with 97% of evaluable tumors testing positive, in contrast with mirvetuximab soravtansine-gynx (Elahere), which was most active in folate receptor alpha–high disease. Neutropenia was the primary toxicity concern, occurring in 87% of patients at 5.8 mg/kg, and granulocyte colony-stimulating factor prophylaxis was strongly recommended.

Refining Patient Selection for PSMA-Targeted Therapy in Prostate Cancer: Jeremie Calais, MD, PhD

Jeremie Calais, MD, PhD, of Gustave Roussy and Université Paris-Saclay, explored how patient selection for therapies targeting prostate-specific membrane antigen (PSMA) in prostate cancer could move beyond a binary PSMA positron emission tomography (PET) result. Although clinical trials and regulators required a positive-or-negative classification, Calais explained that PSMA expression existed on a continuum, with lesions in the same patient showing widely different levels of uptake. He described PSMA PET as a whole-body map that could reveal uniform, patchy, or highly heterogeneous uptake, and noted that extensive vs smaller-volume PSMA-positive disease carried distinct prognostic implications. Calais added that undetectable circulating tumor DNA (ctDNA) was a favorable finding and that understanding of ctDNA features associated with response had expanded. He also highlighted fluorodeoxyglucose PET as a complementary tool that could identify aggressive, highly glycolytic lesions not visible on PSMA PET.

The Feasibility of Lifileucel in Select Metastatic Sarcomas: Lauren Banks, MD, PhD

Lauren Banks, MD, PhD, of Memorial Sloan Kettering Cancer Center, detailed feasibility results from a phase 1 pilot trial (NCT05607095) of the tumor-infiltrating lymphocyte (TIL) therapy lifileucel (Amtagvi) in patients with metastatic or unresectable dedifferentiated liposarcoma or undifferentiated pleomorphic sarcoma, presented at the 2026 SITC Annual Meeting. Patients underwent surgical tumor harvest followed by lymphodepleting chemotherapy, TIL infusion, and interleukin-2. The primary feasibility end point was met, with 11 of 13 patients who underwent surgery proceeding to infusion; 2 of the infused patients received out-of-specification product following risk-benefit discussions. Although the study was not designed to assess efficacy, Banks noted that an activity signal emerged in a small number of patients, which the multicenter phase 2 SARATOGA trial (NCT07741877) was designed to formally evaluate. She added that because the therapy carried substantial toxicity, investigators were analyzing biomarkers of response and loss of response to better identify likely responders.