Immuno-Oncology and Novel Cell Therapies Set Transformation in Motion for Gynecologic Oncology: With Ursula A. Matulonis, MD; and Rebecca Porter, MD, PhD

From Discovery to Delivery: Charting Progress in Gynecologic Oncology, hosted by Ursula A. Matulonis, MD, brings expert insights into the most recent breakthroughs, evolving standards, and emerging therapies across gynecologic cancers. Dr Matulonis is chief of the Division of Gynecologic Oncology and the Brock-Wilcon Family Chair at the Dana-Farber Cancer Institute, as well as a professor of medicine at Harvard Medical School, both in Boston, Massachusetts.

In this episode, Dr Matulonis sat down with guest Rebecca Porter, MD, PhD. Dr Porter is a physician at Dana-Farber Cancer Institute and an assistant professor of medicine at Harvard Medical School.

Drs Matulonis and Porter discussed the evolving role of immunotherapy in gynecologic cancer management, focusing on recent clinical breakthroughs and future directions. They noted that although high-grade serous ovarian cancer has historically been refractory to immunotherapy, the phase 3 KEYNOTE-B96 trial (NCT05116189) demonstrated an efficacy benefit with the addition of pembrolizumab to weekly paclitaxel for patients with platinum-resistant disease. In particular, improvements in overall survival were noted in the PD-L1–positive patient population. Dr Porter attributed this success to the metronomic weekly dosing of paclitaxel, which may increase neoantigen levels and favorably alter the tumor microenvironment (TME).

Moreover, the experts highlighted how immunotherapy has already become the standard of care for patients with mismatch repair–deficient advanced or recurrent endometrial cancer. However, they explained that for the mismatch repair–proficient population, this benefit is less clear and appears most significant in patients with measurable disease or specific molecular subtypes. They added that although circulating tumor DNA (ctDNA) assay results correlate with treatment outcomes, ctDNA is currently not an actionable biomarker for determining treatment duration or selection.

Lastly, Drs Matulonis and Porter reported that the field of gynecologic oncology is shifting toward combination therapies and novel platforms beyond standard checkpoint inhibitors. Treatment advances include bispecific and trispecific antibodies that engage multiple cell types or signals; as well as adoptive cellular therapies, such as CAR T-cell and CAR natural killer–cell therapies. Ultimately, the experts concluded that the goal of managing challenging-to-treat diseases like ovarian cancer is to use combinatorial approaches—incorporating vaccines, anti-angiogenic therapies, and chemotherapy—to overcome the immunosuppressive nature of the TME.