Pembrolizumab offers significantly improved overall survival as a second-line therapy for patients with metastatic esophageal cancer and high PD-L1 expression compared with chemotherapy, according to a phase III study. Pembrolizumab was not significantly better in unselected patients, or in patients with squamous cell histology.
Advanced or metastatic esophageal cancer remains among the most common cancers worldwide, according to Takashi Kojima, MD, of the National Cancer Center Hospital East in Kashiwa, Japan. He presented results of the KEYNOTE-181 trial at the American Society of Clinical Oncology (ASCO) 2019 Gastrointestinal Cancers Symposium, held January 17–19 in San Francisco (Abstract 2).
The study included a total of 628 patients, randomized to receive either pembrolizumab or investigator’s choice chemotherapy (paclitaxel, docetaxel, or irinotecan). It had three prespecified primary endpoints: overall survival (OS) in the intent-to-treat population, OS in the squamous cell carcinoma (SCC) group (401 patients), and OS in the patients with a programmed death ligand 1 (PD-L1) combined positive score (CPS) ≥ 10 (222 patients). Because of the three endpoints, the requirements for statistical significance were adjusted to reduce the possibility of a positive result occurring by chance.
In the intent-to-treat population, the median OS was 7.1 months in both groups, for a hazard ratio (HR) of 0.89 (95% CI, 0.75–1.05; P = .0560). Patients with SCC saw what Kojima described as a “clinically meaningful” improvement in OS, but this did not reach significance, at 8.2 months vs 7.1 months with chemotherapy, for an HR of 0.78 (95% CI, 0.63–0.96; P = .0095).
In those with a PD-L1 CPS ≥ 10, the median OS was 9.3 months with pembrolizumab, compared with 6.7 months with chemotherapy, for an HR of 0.69 (95% CI, 0.52–0.93; P = .0074); this did cross the prespecified threshold for statistical significance.
Pembrolizumab was better tolerated, with 64% of patients experiencing any treatment-related adverse events compared with 86% of chemotherapy patients. The same was true for grades 3–5 treatment-related adverse events (18% vs 41%).
“Data suggest that pembrolizumab should be considered a new standard of care in the second line for patients with metastatic esophageal cancer and PD-L1 CPS ≥ 10,” Kojima concluded.
Harry H. Yoon, MD, of the Mayo Clinic in Rochester, Minnesota, was the discussant for the study, and he said these results have “potentially immediate clinical impact,” though the statistical design of the study does make interpretation somewhat difficult. He said that based on these results, pembrolizumab is not indicated in unselected patients in this setting, but that these data do suggest those with higher PD-L1 expression can benefit. “The efficacy and toxicity results are impressive,” he said, adding that the improved toxicity over chemotherapy should be considered by guidelines committees in the future.