Dr Zamarin on Recent Updates in Endometrial Cancer

Dmitriy Zamarin, MD, PhD, section head, Gynecologic Medical Oncology, member, the Icahn Genomics Institute, member, the Precision Immunology Institute, the Tisch Cancer Institute at Icahn School of Medicine, Mount Sinai, discusses the most recent advances in gynecologic cancer management, particularly in endometrial cancer.

Reflecting on recent strides in gynecologic cancer treatment, particularly those that have been achieved within the past 6 months, prompts a discussion on the developments deemed most influential in shaping clinical practice, Zamarin begins. Commencing with endometrial cancer, notable excitement has surrounded advancements in the past year. Specifically, the combination of PD-1 inhibitors, including pembrolizumab (Keytruda) and dostarlimab-gxly (Jemperli), alongside upfront chemotherapy in patients with advanced endometrial cancer has set new treatment benchmarks, he elucidates. These therapeutic approaches have become standard practice, particularly for patients with mismatch repair–deficient endometrial cancers, Zamarin states.

However, challenges persist for patients with the more prevalent mismatch repair–proficient subtype of endometrial cancer, according to Zamarin. Although some data indicate the potential benefits of incorporating immunotherapy agents into the treatment armamentarium for this disease subset, discerning which patients derive the most benefit remains challenging, he emphasizes, adding that the existing body of research provides a springboard for further exploration into biomarkers within this patient cohort, leveraging existing patient samples to address these lingering questions in the years ahead.

Moreover, notable strides have been made in endometrial cancer management through the exploration of antibody-drug conjugates (ADCs), Zamarin continues. Although awaiting FDA approval for patients with endometrial cancer, these agents have demonstrated promising results by targeting various surface markers on endometrial cancer cells, he says. Among these, fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu), a HER2-targeted ADC, has shown significant activity in high-grade endometrial cancer, such as carcinosarcoma, where treatment options are typically limited, Zamarin says.

T-DXd has already earned recognition in the National Comprehensive Cancer Network Guidelines as a viable treatment option for patients with endometrial cancer. Anticipation mounts for forthcoming data with other ADCs targeting HER2 and other markers, such as B7-H4 and TROP2, heralding a promising frontier in endometrial cancer therapeutics, he concludes.