FDA Approves Pembrolizumab With Chemotherapy in Advanced Endometrial Carcinoma

The FDA approved pembrolizumab (Keytruda; Merck) plus carboplatin and paclitaxel, followed by single-agent pembrolizumab, in adult patients with primary advanced or recurrent endometrial carcinoma, the agency announced today.¹

Pembrolizumab plus carboplatin and paclitaxel is now approved for adult patients with primary advanced or recurrent endometrial carcinoma. | Image credit: wladimir1804 - stock.adobe.com

The approval was based on findings from the phase 3 KEYNOTE-868/NRG-GY018 (NCT03914612), a randomized, double-blind, placebo-controlled trial assessing the addition of pembrolizumab, an anti–PD-1 therapy, to usual chemotherapy in patients with advanced or recurrent endometrial carcinoma.²

The trial patients with stage III or IV disease or stage IVB recurrent disease were assigned in a randomized 1:1 fashion to receive either pembrolizumab or a placebo with paclitaxel plus carboplatin.³ Patients were separated into 2 cohorts based on whether their disease was mismatch repair–deficient (dMMR; n = 222) or mismatch repair–proficient (pMMR; n = 588), and 1:1 randomization to treatment regimens was done within those cohorts.

The main end point in the trial was investigator-assessed progression-free survival (PFS), which was based on RECIST 1.1 criteria.

PFS was not reached in the dMMR cohort, but the estimated PFS for patients treated with pembrolizumab plus chemotherapy during the 12-month analysis was 74%, while those who received chemotherapy plus placebo experienced an estimated PFS of 38% (HR, 0.30; 95% CI, 0.19-0.48; P < .001). In the pMMR cohort, median PFS was 13.1 months among patients treated with pembrolizumab plus chemotherapy and 8.7 months in the placebo cohort (HR, 0.54; 95% CI, 0.41-0.71; P < .001).

"This is the first phase 3 trial to statistically evaluate an anti-PD-1 immunotherapy plus chemotherapy combination in patients with pMMR and dMMR tumors as two independent cohorts,” Ramez Eskander, MD, principal investigator, associate professor in the Department of Obstetrics, Gynecology, and Reproductive Services at the University of California San Diego School of Medicine and gynecologic oncologist at Moores Cancer Center at University of California San Diego Health, said in a statement.⁴ “The addition of pembrolizumab to chemotherapy represents a new frontline therapeutic option for patients with primary advanced or recurrent endometrial carcinoma, demonstrating a statistically significant and clinically meaningful progression-free survival benefit compared to chemotherapy alone, regardless of mismatch repair status.”

In the immunotherapy cohort, patients received 6 cycles of therapy including paclitaxel and carboplatin plus 200 mg of pembrolizumab every 3 weeks plus, followed by up to 14 cycles of maintenance therapy with 400 mg of pembrolizumab every 6 weeks. Those in the placebo cohort received 6 cycles of chemotherapy plus placebo every 3 weeks, then a placebo every 6 weeks for up to 14 cycles.

Adverse reactions associated with the immunotherapy combination were generally consistent with those already reported previously, although rash was more common in the pembrolizumab arm.

The FDA granted priority review to the supplemental biologics license application (sBLA) for pembrolizumab plus chemotherapy in this patient population in February 2024.⁵ The approval marks the third endometrial cancer indication for pembrolizumab in the US and makes pembrolizumab the first immunotherapy indicated for frontline endometrial cancer regardless of MMR status.

“Endometrial cancer is now the most common gynecologic cancer in the US, and deaths from the disease are projected to surpass deaths from ovarian cancer in 2024, underscoring the need for treatment advances for more patients,” said Gursel Aktan, MD, PhD, vice president of global clinical development at Merck Research Laboratories, said.⁴ “This approval represents the first and only anti-PD-1-based option for adult patients with primary advanced or recurrent endometrial carcinoma regardless of mismatch repair status, building on the established role of [pembrolizumab] in certain types of advanced endometrial carcinoma as monotherapy and in combination with [lenvatinib].”

References

1. FDA approves pembrolizumab with chemotherapy for primary advanced or recurrent endometrial carcinoma. News release. FDA. June 17, 2024. Accessed June 17, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-chemotherapy-primary-advanced-or-recurrent-endometrial-carcinoma

2. Testing the addition of the immunotherapy drug pembrolizumab to the usual chemotherapy treatment (paclitaxel and carboplatin) in stage III-IV or recurrent endometrial cancer. ClinicalTrials.gov. Updated May 16, 2023. Accessed June 17, 2024. https://www.clinicaltrials.gov/study/NCT03914612

3. Eskander RN, Sill MW, Beffa L, et al. Pembrolizumab plus chemotherapy in advanced endometrial cancer. N Engl J Med. 2023;388(23):2159-2170. doi:10.1056/NEJMoa2302312

4. FDA approves Merck’s Keytruda (pembrolizumab) plus carboplatin and paclitaxel as treatment for adult patients with primary advanced or recurrent endometrial carcinoma. News release. June 17, 2024. Accessed June 17, 2024. https://www.merck.com/news/fda-approves-mercks-keytruda-pembrolizumab-plus-carboplatin-and-paclitaxel-as-treatment-for-adult-patients-with-primary-advanced-or-recurrent-endometrial-carcinoma/

5. FDA grants priority review to Merck’s application for Keytruda (pembrolizumab) plus chemotherapy as treatment for primary advanced or recurrent endometrial carcinoma. News release. Merck. February 20, 2024. Accessed June 17, 2024. https://www.merck.com/news/fda-grants-priority-review-to-mercks-application-for-keytruda-pembrolizumab-plus-chemotherapy-as-treatment-for-primary-advanced-or-recurrent-endometrial-carcinoma/