Pembrolizumab Indications Expand to Include Cervical Cancer

June 13, 2018

Yesterday, the FDA announced that it has expanded the indications of pembrolizumab (Keytruda) to include recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1.

Yesterday, the FDA announced that it has expanded the indications of pembrolizumab (Keytruda) to include recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1.

This indication was approved by the FDA after pembrolizumab had previously been granted priority review based on tumor response rate and durability of response. In addition to cervical cancer, pembrolizumab’s indications include approval as a first-line treatment in patients with metastatic non—small cell lung cancer as well as unresectable or metastatic melanoma.

“Keytruda is now the first anti-PD-1 therapy approved for the treatment of advanced cervical cancer, providing an important new second-line option for certain patients with this disease,” said Roy Baynes, MD, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, in a prepared statement. “This approval also marks the first indication for Keytruda in a gynecologic cancer and reflects our ongoing commitment to bring forward innovative treatment options across a broad range of cancers, including cancers that disproportionately affect women.”

The approval was based on results from the KEYNOTE-158 trial, in which 98 patients with recurrent or metastatic cervical cancer were enrolled in a multicenter, nonrandomized, open-label, multicohort trial. Participants were treated with 200mg of pembrolizumab delivered intravenously every 3 weeks until they showed either unsafe levels of toxicity or documented disease progression. Patients without disease progression could be treated for up to 24 months, and a tumor status assessment was completed every 9 weeks for the first 12 months, and every 12 weeks thereafter.

Within the trial, 77 patients had tumors that expressed PD-L1 with a combined positive score of 1 or greater. The objective response rate was 14.3% (95% CI, 7.4%-24.1%), with a complete response rate of 2.6% and partial response rate of 11.7%. Among 11 patients who responded, median diagnostic odds ratio was not yet reached (ranged from 4.1-18.6+ months), and 91% of patients had a response duration of 6 months or longer.

Overall, the most common adverse events reported that occurred in at least 20% of patients were fatigue, musculoskeletal pain, diarrhea, pain and abdominal pain, and decreased appetite. In addition, 8% of patients had to discontinue treatment due to adverse events. Serious adverse events occurred in 39% of patients, the most serious of which were anemia, fistula, hemorrhage, and infections.

“Even with the many advances observed across gynecologic cancers, new treatment options have been lacking for previously treated patients with advanced cervical cancer. The 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,” said Bradley Monk, MD, oncologist at Arizona Oncology, medical director of US Oncology Research Gynecology Program, in a statement.

Today, the FDA announced that it has granted pembrolizumab accelerated approval for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or for patients who have relapsed after 2 or more lines of prior therapy. The approval was based on data from 53 patients with relapsed or refractory PMBCL that participated in KEYNOTE-170, a multicenter open-label single-arm trial. Additionally, pembrolizumab received orphan product designation and breakthrough therapy designation for this indication; however, "continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials," according to a statement from the FDA.