FDA grants full approval to pembrolizumab for MSI-H/dMMR solid tumors, including genitourinary cancers

The FDA has made pembrolizumab (Keytruda) a permanent fixture in the armamentarium for the treatment of patients with microsatellite instability–high (MSI-H) or mismatch repair–deficient (dMMR) solid tumors, including prostate and other genitourinary cancers.¹

For the 380 patients with MSI-H/dMMR non-CRC solid tumors, including genitourinary cancers, the ORR was 33%, with a DOR that ranged from 1.9+ months to 63.9+ months.

The indication, which is for patients with unresectable or metastatic tumors who have progressed following previous treatment and who have no satisfactory alternative options, converts the 2017 accelerated approval of the immunotherapy pembrolizumab in this setting to a full approval.

The conversation to permanent approval was based on a pooled analysis of 504 adult and pediatric patients with over 30 types of cancer enrolled across three phase 2 trials: KEYNOTE-158 (NCT02628067), KEYNOTE-164 (NCT02460198), and KEYNOTE-051 (NCT02332668). The KEYNOTE-158 population comprised patients with non–colorectal cancer (CRC), including prostate cancer, bladder cancer, and renal cell carcinoma.

The pooled analysis showed that at 20.1 months’ median follow-up (range, 0.1-71.4), pembrolizumab reached an objective response rate (ORR) of 33.3% (95% CI, 29.2%-37.6%), which consisted of a 10.3% complete response rate and a 23.0% partial response rate.

The median duration of response (DOR) was 63.2 months (range, 1.9+ to 63.9+). Among the responders, 77% had a response duration of at least 12 months, and 39% had responses lasting 36 months or longer.

“This approval reinforces the important role of Keytruda in certain patients with MSI-H or dMMR solid tumors facing a variety of cancers,” Luis A. Diaz, Jr., MD, head of the Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, stated in a press release. “These data also further underscore the need for biomarker testing to identify patients who may be eligible for this therapy.”

Additional supporting data

The pooled analysis included 124 patients from the KEYNOTE-164 trial. These patients had advanced MSI-H/dMMR CRC that progressed after fluoropyrimidine and oxaliplatin or irinotecan with or without a VEGF/EGFR monoclonal antibody–based therapy. An additional 373 patients were included from KEYNOTE-158, which enrolled patientswith advanced MSI-H/dMMR non-CRC who progressed after previous treatment were included. The final 7 patients for the pooled analysis were pediatric patients with MSI-H/dMMR cancers from the KEYNOTE-051 trial.

All patients were treated with intravenous pembrolizumab every 3 weeks with the doses being 200 mg and 2 mg/kg for adult and pediatric patients, respectively. Treatment continued until intolerable toxicity, progressive disease, or up to 24 months.

The median duration of treatment exposure was 6.2 months (range, 1 day-53.5 months) in the KEYNOTE-158 and KEYNOTE-164 trials, and 2.1 months (range, 1 day-25 months) in the KEYNOTE-051 trial.

The ORR was 34% (95% CI, 26%-43%) for the 124 patients with MSI-H/dMMR CRC, with response duration ranging from 4.4 months to over 58.5 months. For the 380 patients with MSI-H/dMMR non-CRC solid tumors, including genitourinary cancers, the ORR was 33% (95% CI, 28%-38%), with a DOR that ranged from 1.9+ months to 63.9+ months.

Immune-mediated adverse events that physicians should monitor for in patients receiving pembrolizumab include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and allogeneic hematopoietic stem cell transplantation complications.

"Today’s approval builds on the 2017 accelerated approval of [pembrolizumab] as the first immunotherapy with a tumor agnostic indication and supports the role of [pembrolizumab] as an effective immunotherapy option based on a pan-tumor predictive biomarker," Scot Ebbinghaus, MD, vice president, global clinical development, Merck Research Laboratories, stated in the press release. “This milestone reflects Merck’s longstanding commitment to biomarker research and personalizing treatment strategies for patients.”

Reference

1. FDA converts to full approval indication for Keytruda (pembrolizumab) for certain adult and pediatric patients with advanced microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors. News release. Merck. March 29, 2023. Accessed March 29, 2023. https://www.merck.com/news/