Pembrolizumab With Chemotherapy Approved for Primary Advanced or Recurrent Endometrial Carcinoma

The FDA has granted approval to pembrolizumab (Keytruda®, Merck) with carboplatin and paclitaxel, followed by single-agent pembrolizumab, for adult patients with primary advanced or recurrent endometrial carcinoma.

Why it matters: “Endometrial cancer is one of only a few malignant conditions for which both incidence and mortality are currently rising,” wrote Ramez Eskander, MD, Assistant Professor of Obstetrics, Gynecology, and Reproductive Sciences at The University of California, San Diego, and colleagues, in their published results of the KEYNOTE-868/NRG-GY018 study (NCT03914612), on which approval was based. “By 2040, it is projected to be the third most prevalent cancer and the fourth leading cause of cancer death among women. Survival for women with uterine cancers has not improved during the past 4 decades, unlike the history of many other solid tumors.”

What they studied: Efficacy was evaluated in the phase 3, double-blind, placebo-controlled trial in which 810 patients with advanced or recurrent endometrial carcinoma were randomized 1:1 to receive either:

  • 200 mg of pembrolizumab every three weeks with 175 mg/m2 of paclitaxel and 5 mg/mL/min of carboplatin AUC for six cycles, followed by 400 mg of pembrolizumab every six weeks for up to 14 cycles
  • Placebo every three weeks with 175 mg/m2 of paclitaxel and 5 mg/mL/min of carboplatin AUC for six cycles, followed by placebo every six weeks for up to 14 cycles

Patients were stratified based on mismatch repair (MMR) status, ECOG performance status— 0 or 1 versus 2—and prior adjuvant chemotherapy. Included in this trial were two cohorts based on MMR status; Cohort 1 included 222 patients with MMR deficiency, and Cohort 2 included 588 patients with MMR proficiency.

The primary efficacy outcome measured was progression-free survival, as assessed by investigator according to RECIST 1.1.

What they found: In the cohort consisting of MMR-deficient patients, the pembrolizumab arm did not reach a median progression-free survival compared with the placebo arm at a median of 6.5 months. In the cohort consisting of MMR-proficient patients, the pembrolizumab arm reached a median progression-free survival of 11.1 months compared with the placebo arm at 8.5 months.

Adverse events: Adverse events associated with individuals receiving pembrolizumab and chemotherapy were generally similar to those previously reported for pembrolizumab or chemotherapy, with the exception of a higher incidence of rash. See the prescribing information for complete adverse events.

Conclusion: “Our results show that pembrolizumab in combination with chemotherapy and continued as maintenance therapy led to significantly longer progression-free survival than placebo in patients with MMR-deficient and MMR-proficient endometrial cancers,” concluded Dr. Eskander and colleagues.

Instructions: The recommended dosage of pembrolizumab is 200 mg every three weeks or 400 mg every six weeks until disease progression, unacceptable toxicity, or up to 24 months.

For More Information

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

Keytruda® (pembrolizumab) prescribing information (2024). Merck. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/125514s155lbl.pdf

Clinicaltrials.gov (2023). Testing the addition of the immunotherapy drug pembrolizumab to the usual chemotherapy treatment (paclitaxel and carboplatin) in stage III-IV or recurrent endometrial cancer. NLM identifier: NCT03914612.

US Food and Drug Administration (2024). FDA approves pembrolizumab with chemotherapy for primary advanced or recurrent endometrial carcinoma. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-chemotherapy-primary-advanced-or-recurrent-endometrial-carcinoma

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