Five Under 5: Top Oncology Videos for the Week of 8/31

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:

Olaparib Plus Temozolomide in Advanced Uterine Leiomyosarcoma: Brian A. Van Tine, MD, PhD

Brian A. Van Tine, MD, PhD, of Washington University School of Medicine, discussed data from the phase 2/3 Alliance A092104 trial (NCT05432791) examining olaparib (Lynparza) plus temozolomide (Temodar) compared with investigator’s choice in patients with advanced uterine leiomyosarcoma. The investigator’s choice arm, particularly trabectedin (Yondelis) or pazopanib (Votrient), showed a modest progression-free survival (PFS) advantage; the experimental combination faced challenges due to high rates of hematologic toxicity and frequent dose modifications. Van Tine noted that low rates of homologous recombination deficiency and the lack of a CLIA-certified RAD51 foci assay likely limited patient stratification and diluted efficacy signals. Despite these hurdles, some patients still experienced durable responses with the olaparib regimen, highlighting a potential biologically defined subgroup that may benefit from this approach. He emphasized the ongoing need for biomarker-driven strategies and continued research to identify which patients with uterine leiomyosarcoma are most likely to benefit from olaparib/temozolomide.

Potential Future Implications of Botensilimab and Balstilimab in MSS mCRC: Benjamin L. Schlechter, MD

Benjamin L. Schlechter, MD, of Dana-Farber Cancer Institute, spotlighted future directions for botensilimab (AGEN1181) in combination with balstilimab (AGEN2034) for patients with previously treated, microsatellite-stable (MSS) metastatic colorectal cancer (mCRC) without active liver metastases. He emphasized the need to advance FDA approval in the refractory setting through randomized trials, noting compelling early findings. Current studies include the phase 2 NEST-1 (NCT05571293) and UNICORN (EU-CT 2022-501308-90-0) trials, which demonstrated benefit with this approach in earlier-stage disease with no recurrences and negative circulating tumor DNA findings. Schlechter highlighted the potential to move botensilimab into earlier lines of therapy, leveraging in situ primary tumors and lymph nodes to train the immune system and promote responses. Overall, he stressed continued investigation to optimize botensilimab’s role across refractory and earlier-stage mCRC.

MRD Negativity Outcomes With Ponatinib vs Imatinib in Newly Diagnosed Ph+ ALL: Ibrahim Aldoss, MD

Ibrahim T. Aldoss, MD, of City of Hope, discussed minimal residual disease (MRD) outcomes in patients with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) treated with ponatinib (Iclusig) or imatinib (Gleevec). In the phase 3 PhALLCON trial (NCT03589326), patients who did not achieve MRD negativity at the end of induction remained on their assigned treatment. By the end of therapy, more patients receiving ponatinib achieved MRD negativity and deep molecular responses vs those on imatinib, with respective MR4.5 rates of 37% vs 10%. Patients remaining on ponatinib also experienced superior 2-year event-free survival (87% vs 62%) and overall survival (OS) vs imatinib. Toxicity profiles were comparable between the arms, with similar rates of treatment-emergent adverse effects and dose modifications.

Rationale for Evaluating Adjuvant Pembrolizumab in Clear Cell RCC: Naomi B. Haas, MD

Naomi B. Haas, MD, of the Hospital of the University of Pennsylvania, shed light on the phase 3 KEYNOTE-564 trial (NCT03142334) evaluating adjuvant pembrolizumab (Keytruda) vs placebo in patients with clear cell renal cell carcinoma (ccRCC). The trial enrolled approximately 1,000 patients who had undergone surgery within 12 weeks and were at intermediate-high or high risk of recurrence. Patients were randomly assigned 1:1 to receive pembrolizumab for up to 17 cycles (n = 496) or placebo (n = 498). The primary end point was disease-free survival per investigator assessment, with OS and safety as key secondary end points. This trial was designed to provide insight into the role of pembrolizumab in the adjuvant setting following nephrectomy in patients with histologically confirmed ccRCC.

Health-Related QOL With Nivolumab Plus Ipilimumab in mCRC: Elena Élez, MD, PhD

Elena Élez, MD, PhD, of Vall d’Hebron University Hospital, discussed quality-of-life (QOL) data from the phase 3 CheckMate 8HW trial (NCT04008030) of nivolumab (Opdivo) plus ipilimumab (Yervoy) vs nivolumab in patients with microsatellite instability-high metastatic colorectal cancer. Patients receiving the combination (n = 296) showed a significant PFS benefit vs single-agent nivolumab (n = 286; HR, 0.62; 95% CI, 0.48-0.81; P = .0003). QOL measures indicated a numerical improvement with the doublet, with global health status and physical functioning scores trending higher starting at week 7 and exceeding minimally important changes by week 21. Fatigue scores also improved earlier in the combination arm vs the monotherapy arm. These data suggest that adding ipilimumab did not negatively impact QOL, despite the potential for increased toxicity.