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Pembrolizumab extends OS in PD-L1-expressing esophageal cancers
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A randomized phase 3 trial designed to compare pembrolizumab with chemotherapy as second-line treatment of advanced or metastatic esophageal or esophagogastric junction carcinoma met its primary endpoint of OS among patients whose disease expressed PD-L1.
Pembrolizumab (Keytruda, Merck) is the first anti-PD-1 therapy to demonstrate a survival benefit in this population, according to the agent’s manufacturer.
The KEYNOTE-181 trial included more than 600 patients with advanced or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus, or Siewert type I adenocarcinoma of the esophagogastric junction that progressed after standard first-line therapy.
Researchers randomly assigned patients 1:1 to pembrolizumab 200 mg every 3 weeks or investigator’s choice of IV chemotherapy. Chemotherapy regimens included docetaxel (75 mg/m2 on day 1 of each 21-day cycle), paclitaxel (80 mg/m2 to 100 mg/m2 on days 1, 8 and 15 of each 28-day cycle), or irinotecan (80 mg/m2 on day 1 of each 14-day cycle).
OS in the entire cohort and in two subgroups — patients with a PD-L1 combined positive score (CPS) of 10 or higher and those with squamous cell carcinoma — served as the primary endpoint. Secondary endpoints included PFS, objective response rate and safety/tolerability.
Results showed pembrolizumab conferred a statistically significant improvement in OS compared with chemotherapy among patients with CPS of 10 or greater, regardless of histology.
The OS improvement observed with pembrolizumab in the intention-to-treat population and the subgroup with squamous cell histology did not reach statistical significance.
Per the statistical analysis plan, investigators did not formally test PFS or ORR because a significant OS benefit was not observed in the intention-to-treat population.
The safety profile of pembrolizumab appeared consistent with that observed in prior studies.
Complete results of KEYNOTE-181 will be presented at an upcoming meeting.
“We are encouraged by these results of Keytruda as monotherapy in previously-treated patients, and look forward to continuing our research efforts in this significant area of unmet need with our ongoing phase 3 trial, KEYNOTE-590, evaluating Keytruda in combination with chemotherapy as a first-line treatment for patients with esophageal carcinoma,” Roy Baynes, MD, PhD, senior vice president, head of global clinical development and chief medical officer at Merck Research Laboratories, said in a company-issued press release.