The checkpoint inhibitor pembrolizumab conferred a durable tumor response in patients with advanced cervical cancer, who were positive for programmed death ligand 1 (PD-L1).
Among 98 patients, all of whom had progressed despite prior treatment, overall response rate was 12.2% (95% confidence interval, 6.5%-20.4%), with three complete and nine partial responses. All 12 responses were in patients with PD-L1-positive tumors, wroteand his colleagues. The report is in the .
The response curve had not peaked by the end of follow-up, suggesting further benefit of the antibody, said Dr. Chung of Yonsei Cancer Center, Seoul, South Korea. On the basis of these data, firstat the 2018 meeting of the American Society of Clinical Oncology, the Food and Drug Administration the antibody for advanced cervical cancer last year.
“These results show that treatment with pembrolizumab offers a clinically meaningful therapeutic option for a subset of patients with previously treated advanced cervical cancer,” the researchers said. The approval makes pembrolizumab the first immunotherapy approved for the treatment of an advanced gynecologic malignancy.
The phase 2 KEYNOTE-158 study comprised 98 women (median age 46 years) with advanced cervical cancer with progression after chemotherapy. All received pembrolizumab 200 mg every 3 weeks for 2 years or until progression, intolerable toxicity, or physician or patient decision.
Most of the patients (83.7%) were positive for PD-L1. All had received at least one or more lines of chemotherapy before entering the study. The median follow-up was 10 months and the median treatment duration 2.9 months, with a range of 1 day-22 months.
By the study’s end, most patients (85.7%) had experienced disease progression or had died. Overall survival was poor even in the PD-L1-positive patients, with 82.9% experiencing progression or death. Overall mortality was 69.4% and 64.6%, respectively. However, PD-L1 patients did live longer, a median of 11 months, compared with 9.4 months in the entire cohort.
At 6 months, overall survival estimates were 75.2% in the total cohort and 80.2% in the PD-L1 patients; 12-month overall survival estimates were 41.4% and 47.3%, respectively.
However, among the 12 responders with PD-L1-postitive tumors, just one had died by the data cutoff, suggesting that longer treatment with pembrolizumab could be beneficial in this group.
“Responses typically occurred within 2.1 months and were durable, with a median duration of response that had not been reached after a median follow-up of 10.2 months and an estimated 90.9% of responses ongoing at 6 months” Dr. Chung and his colleagues wrote.
Adverse events were common (65.3%) with 12.2% graded as serious. But none were lethal, and only four patients discontinued pembrolizumab because of a treatment-related adverse event.
“Our results from an interim analysis of data from the phase II KEYNOTE-158 clinical trial show that pembrolizumab has promising antitumor activity in patients with previously treated advanced cervical cancer,” the researchers said. “These response rates are similar or superior to those observed with other treatment options in this setting.”
Pembrolizumab is now beingin combination with concurrent chemoradiotherapy and concurrent versus sequential chemoradiotherapy.
Merck & Co. sponsored the study.
SOURCE: Chung HC et al. J Clin Oncol. 2019 April 3. .