First-line pembrolizumab monotherapy met the primary end point of PFS in dMMR advanced/recurrent endometrial cancer.
Pembrolizumab (Keytruda) monotherapy significantly improved progression-free survival (PFS) compared with platinum doublet chemotherapy in patients with mismatch repair deficient (dMMR) advanced or recurrent endometrial cancer who had not previously received systemic chemotherapy or who experienced recurrence more than 6 months after completing prior adjuvant therapy, meeting the primary end point of the phase 3 KEYNOTE-C93 trial (NCT05173987).1
At a prespecified interim analysis conducted by an independent data monitoring committee, a trend toward improvement in overall survival (OS) was also observed with pembrolizumab, although OS data were not mature at the time of analysis. The trial is ongoing, and OS will be assessed in the full study population at a future analysis. Data from the interim analysis also showed a clinically meaningful overall response rate (ORR), complete response rate (CRR), and duration of response (DOR) favoring pembrolizumab. The safety profile of pembrolizumab in KEYNOTE-C93 was consistent with that observed in previously reported studies, and no new safety signals were identified.
"This is the first phase 3 trial of a PD-1 inhibitor to show improved PFS compared with platinum doublet chemotherapy when given as monotherapy in the frontline setting for these patients, potentially providing a chemo-free option," Brian Slomovitz, MD, the director of Gynecologic Oncology and deputy director of the Braman Comprehensive Cancer Center at Mount Sinai Medical Center in Miami Beach, Florida, and the study's overall principal investigator, said in a news release.
KEYNOTE-C93 is a randomized, open-label phase 3 trial evaluating pembrolizumab monotherapy vs carboplatin plus paclitaxel in patients with dMMR advanced or recurrent endometrial cancer who had not received prior systemic chemotherapy, or who experienced recurrence more than 6 months after completing adjuvant therapy.1,2
The trial enrolled 299 patients, who were randomly assigned to pembrolizumab at 400 mg intravenously every 6 weeks for up to 18 cycles or paclitaxel at 175 mg/m2 plus carboplatin (AUC 5 or 6) every 3 weeks for 6 cycles.
The trial's coprimary end points are PFS per blinded independent central review by RECIST 1.1 criteria and OS. ORR represents a key secondary end point.
In the United States, pembrolizumab holds 3 indications in endometrial carcinoma. It is approved in combination with carboplatin and paclitaxel, followed by pembrolizumab as a single agent, in primary advanced or recurrent endometrial carcinoma. It is also approved in combination with lenvatinib (Lenvima) in advanced endometrial carcinoma that is mismatch repair proficient or not microsatellite instability-high (MSI-H), in patients with disease progression following prior systemic therapy who are not candidates for curative surgery or radiation. As a single agent, pembrolizumab is approved in advanced endometrial carcinoma that is MSI-H or dMMR under the same progression and surgical-candidacy criteria.¹
“These findings build upon the well-established role of [pembrolizumab] in endometrial cancer, one of the few cancers with rising incidence rates,” said Gursel Aktan, MD, PhD, vice president, global clinical development, Merck Research Laboratories. “We are committed to helping women facing this disease by advancing potential treatment options. We thank the patients and investigators for their important contributions to this study and look forward to sharing these results with the medical community.”
