Five Under 5: Top Oncology Videos for the Week of 9/21

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:

FDA Approval of Subcutaneous Pembrolizumab in Solid Tumors: J.Thaddeus Beck, MD, FACP

J. Thaddeus Beck, MD, FACP, of Highlands Oncology Group, discussed the FDA approval of subcutaneous pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) for adult and pediatric (≥12 years) solid tumors already approved for IV pembrolizumab (Keytruda). The decision was supported by findings from the phase 3 3475A-D77 study (NCT05722015), which showed subcutaneous pembrolizumab plus chemotherapy had similar pharmacokinetics, efficacy, and safety to that of IV administration. Objective response rates (ORRs) with the respective approaches were 45% and 42%, respectively. Beck noted that subcutaneous dosing takes seconds rather than an hour or more, reducing chair time, and most patients in the study preferred this route. The subcutaneous formulation allows treatment to be tailored to patients without compromising effectiveness or tolerability, while easing scheduling and clinic flow. Beck concluded that subcutaneous pembrolizumab broadens delivery options, preserves its clinical profile, and supports patient-centered care.

Potential Role for Sac-TMT With/Without Pembrolizumab in HR+, HER2– Breast Cancer: Sara M. Tolaney, MD, MPH

Sara M. Tolaney, MD, MPH, of Dana-Farber Cancer Institute and Harvard Medical School, discussed the potential of the antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT) as monotherapy or combined with pembrolizumab (Keytruda) for patients with HR-positive, HER2-negative unresectable or metastatic breast cancer. The phase 3 TroFuse-010 trial (NCT06312176) is enrolling approximately 1,200 patients who are randomized to sac-TMT alone, sac-TMT plus pembrolizumab, or physician’s choice of chemotherapy, with progression-free survival per RECIST 1.1 criteria as the primary end point. If successful, sac-TMT could become a frontline ADC option for this population, complementing existing agents such as fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu), which is limited to patients with some HER2 expression. Tolaney emphasized the promise of an immunotherapy option in this setting and suggested that combining an ADC with a checkpoint inhibitor could further improve outcomes.

Gemcitabine and Nab-Paclitaxel in Treatment-Naive, Older Pancreatic Cancer: Efrat Dotan, MD

Efrat Dotan, MD, of Ann B. Barshinger Cancer Institute at Penn Medicine Lancaster General Health, discussed the phase 2 ECOG-ACRIN EA2186 (GIANT) trial (NCT04233866), which evaluated gemcitabine and nab-paclitaxel (Abraxane) vs 5-fluorouracil (5-FU), leucovorin, and liposomal irinotecan in older patients with treatment-naive, metastatic pancreatic cancer. The trial enrolled patients aged 70 years or older with geriatric vulnerabilities, who were randomly assigned to receive modified gemcitabine/nab-paclitaxel or dose-reduced 5-FU plus leucovorin and liposomal irinotecan. Findings showed minimal differences in efficacy, with median overall survival (OS) of 4.7 months in the gemcitabine/nab-paclitaxel arm and 4.4 months in the 5-FU arm. Toxicity rates were largely similar, with higher neuropathy in the gemcitabine/nab-paclitaxel arm and more diarrhea in the 5-FU arm. Dotan noted that patients who remained on treatment for at least 4 weeks experienced a median OS of 8.0 months, suggesting that doses can be attenuated while maintaining outcomes.

Role of S100A8/A9 in Promoting T-Cell Exhaustion in Multiple Myeloma: Oliver Van Oekelen, MD, PhD

Oliver Van Oekelen, MD, PhD, of Icahn School of Medicine at Mount Sinai, discussed findings on the role of S100A8/A9 in limiting responses to bispecific antibody therapy in multiple myeloma. In patient sample analyses, higher serum levels of S100A8/A9 were linked with a lower likelihood of achieving a very good partial response and correlated with poorer progression-free survival. In vitro studies showed that T cells exposed to elevated S100A8/A9 exhibited exhaustion, with reduced cytokine production and diminished cytotoxic activity against myeloma cells. Preclinical models showed that blocking S100A8/A9 restored T-cell function, improving cytokine production and cytotoxicity in the presence of bispecific antibodies. Van Oekelen highlighted these data as evidence that S100A8/A9 may serve as both a biomarker of resistance and a potential therapeutic target to enhance T-cell–directed immunotherapies.

Teclistamab-Based Regimens in Newly Diagnosed Multiple Myeloma: Marc S. Raab, MD

Marc S. Raab, MD, of of Heidelberg Myeloma Center, Heidelberg University Hospital, discussed post-induction outcomes and minimal residual disease (MRD) analysis from the phase 2 MajesTEC-5 trial (NCT05695508) of teclistamab-cqyv (Tecvayli) in patients with newly diagnosed multiple myeloma. Those receiving teclistamab with daratumumab (Darzalex) and lenalidomide (Revlimid; Tec-DR; arm A), Tec-DR with teclistamab every 4 weeks (arm A1), or teclistamab plus daratumumab, bortezomib (Velcade), and lenalidomide (Tec-DVR; arm B) achieved ORRs of 100%. Complete response (CR) rates in the respective arms were 100%, 95%, and 73.7%. MRD negativity at a threshold of 10^-5 was observed in all patients with available samples at the end of cycle 3, confirmed at cycle 6. Overall, the cumulative MRD negativity rate across all arms was 98% by the end of induction.