Role of Biomarkers in Choosing Advanced Endometrial Cancer Treatment

Bhavana Pothuri, MD, professor in the Department of Obstetrics and Gynecology and Department of Medicine at NYU Grossman School of Medicine, and director of Gynecologic Oncology Clinical Trials at NYU Langone Health’s Perlmutter Cancer Center, discusses the importance of determining biomarkers of patients with endometrial cancer to decide on treatment options.

According to Pothuri, there are several classifications of endometrial cancer, including microsatellite instability-high (MSI-H) and deficient mismatch repair (dMMR), that influence the efficacy of later lines of treatment following first-line platinum-based chemotherapy. Approximately 25% to 30% of patients with endometrial cancer have dMMR tumors. Immunohistochemistry can identify dMMR, while polymerase chain reaction (PCR) testing or next-generation sequencing (NGS) can determine the degree of microsatellite instability, Pothuri stated.

Dostarlimab (Jemperli), an anti-PD-1 monoclonal antibody, was approved by the FDA in April 2021 for patients with advanced or recurrent dMMR endometrial tumors following a 42.3% overall response rate (ORR) in the phase 1 GARNET trial (NCT02715284). The phase 2 KEYNOTE-158 trial (NCT02628067) of pembrolizumab (Keytruda) showed a 48% ORR in patients with heavily pretreated, advanced MSI-H or dMMR endometrial cancer, and the FDA is currently reviewing the application for use of pembrolizumab for this population based on these data.

For patients with advanced endometrial cancer that is not MSI-H or dMMR, a combination of pembrolizumab and lenvatinib (Lenvima) was approved in July 2021 based on the results of the phase 3 KEYNOTE-775 trial (NCT03517449).

TRANSCRIPTION:

0:08 | It's really important at minimum to classify tumors as either MSI-H, dMMR, or microsatellite stable. And this can be done with immunohistochemistry for the mismatch repair proteins, or MSI testing, which can be done by PCR testing of 5 distinct microsatellite loci, or through tumor NGS of the microsatellite loci and assessment of tumor mutation burden or TMB. The reason I say that this is important is because the treatment of first recurrence after chemotherapy has—the landscape and treatment paradigm has been completely evolving. And at present, if a tumor is MSI-H or dMMR, pembrolizumab, based on the KEYNOTE-158 data, or dostarlimab, which is based on the GARNET data, are 2 [immune] checkpoint inhibitors that have shown to be pretty efficacious with response rates of 45% to 50%. Both of these agents have received FDA accelerated approval.