FDA OKs Keytruda for Relapsed/Refractory PMBCL, Advanced Cervical Cancer

Pembrolizumab (Keytruda, Merck) gained FDA approval for 2 new oncology indications.

Officials with the FDA have granted accelerated approval to pembrolizumab (Keytruda, Merck) for 2 new indications, including the treatment of refractory primary mediastinal large B-cell lymphoma (PMBCL), and recurrent metastatic cervical cancer in previously treated patients whose tumors express PD-L1, according to a press release.

The agency’s approval of pembrolizumab for recurrent metastatic cervical cancer makes it the first anti-PD-1 therapy approved for this patient population, Merck announced in a news release.

For the treatment of PMBCL, pembrolizumab is approved for use in both adult and pediatric patients, and those who have relapsed after 2 or more prior lines of therapy. The approval is based on data from the KEYNOTE-170 trial, which evaluated 53 patients with relapsed or refractory PMBCL. Patients were treated with pembrolizumab 200 mg intravenously every 3 weeks until acceptable toxicity or documented disease progression, or for up to 24 months for patients who did not progress.

According to the data, the overall response rate (ORR) was 45%, including 11% complete responses and 34% partial responses. The median duration of response was not reached within the median follow-up period of 9.7 months, and the median time to first objective response was 2.8 months.

This treatment is not recommended for patients with PMBCL who require urgent cytoreductive therapy.

The recommended dose for the treatment of adults with PMBCL is 200 mg every 3 weeks, and 2 mg/kg (up to a maximum of 200 mg) every 3 weeks for pediatric patients.

The most common adverse events in ³10% of patients with PMBCL treated in KEYNOTE-170 were musculoskeletal pain, upper respiratory tract infection, pyrexia, fatigue, cough, dyspnea, diarrhea, abdominal pain, nausea, arrhythmia, and headache.

According to Merck, pembrolizumab’s indication for recurrent metastatic cervical cancer is based on the KEYNOTE-158 trial, which investigated the efficacy of pembrolizumab in 98 patients with recurrent or metastatic cervical cancer, excluding patients with autoimmune disease or a medical condition that required immunosuppression. Patients were treated with pembrolizumab intravenously at a dose of 200 mg every 3 weeks until acceptable toxicity or documented disease progression. Assessment of tumor status was performed every 9 weeks for the first 12 months, and every 12 weeks thereafter.

Among the 98 patients, 77 had tumors that expressed PD-L1 with a Combined Positive Score (CPS) ³1 and received at least 1 line of chemotherapy in the metastatic setting. Of the 77 patients, the ORR was 14.3% with a complete response rate of 2.6% and partial response rate of 11.7%. Among the 11 responding patients, median duration of response was not yet reached and 91% experienced a duration of response of 6 months or longer. No responses were observed in patients whose tumors did not have a PD-L1 expression.

The most common adverse events associated with pembrolizumab in these patients included fatigue, musculoskeletal pain, diarrhea, pain and abdominal pain, and decreased appetite.

“Even with the many advances observed across gynecologic cancers, new treatment options have been lacking for previously treated patients with advanced cervical cancer,” Bradley Monk, MD, oncologist with Arizona Oncology, medical director of US Oncology Research Gynecology Program, said in the press release. “This approval of Keytruda in this indication is important news—and as an oncologist, it is exciting to see a much needed option made available to these patients.”

References

1. FDA approves pembrolizumab for treatment of relapsed or refractory PMBCL [news release]. FDA’s website. https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm610670.htm?utm_campaign=Oncology%206%2F13%2F2018&utm_medium=email&utm_source=Eloqua&elqTrackId=ce3e8cb7b99142cba3cc1d7c54d4ca4b&elq=5f047105eef5491fbc61687ac5a9000d&elqaid=3898&elqat=1&elqCampaignId=3025. Accessed June 13, 2018.

FDA Approves Merck’s KEYTRUDA® (pembrolizumab) for Previously Treated Patients with Recurrent or Metastatic Cervical Cancer Whose Tumors Express PD-L1 (CPS Greater Than or Equal to 1) [news release]. Merck’s website. http://www.mrknewsroom.com/news-release/oncology/fda-approves-mercks-keytruda-pembrolizumab-previously-treated-patients-recurre. Accessed June 13, 2018.