Treatment with the anti–programmed death-1 (PD-1) antibody pembrolizumab resulted in durable antitumor activity with manageable side effects in patients with heavily pretreated, PD-ligand 1 (PD-L1)-positive advanced esophageal carcinoma, according to phase IB results of the KEYNOTE-028 study published in the Journal of Clinical Oncology.
“Overall, tumor shrinkage from baseline in target lesions occurred in more than half the patients,” wrote Toshihiko Doi, MD, of National Cancer Center East, Japan, and colleagues.
KEYNOTE-028 was an international, multicenter, multi-cohort trial evaluating pembrolizumab in patients with 20 different types of PD-L1–positive advanced solid tumors. Patients were given pembrolizumab 10 mg/kg once every 2 weeks for up to 2 years or until progression, intolerable toxicity, or patient or investigator decision to discontinue. There were 83 patients with esophageal carcinoma and samples evaluable for PD-L1 expression; 37 had PD-L1 positive tumors and 23 were enrolled in the trial.
The median patient age was 65 years and most had squamous cell histology (78%). The majority of patients (87%) had two or more prior therapies for their disease.
At data cutoff, the median follow-up was 7 months. At that time, 39% of patients had treatment-related adverse events, the most common of which were decreased appetite, decreased lymphocyte count, generalized rash, and rash. No grade 4 or worse adverse events, or death, were attributed to pembrolizumab.
The overall response rate was 30%, with a median duration of response of 15 months. Responses occurred in patients with both adenocarcinoma and squamous cell histology. All of the responses were partial responses. Two additional patients had stable disease. The researchers found no pattern for responses related to prior chemotherapy regimen.
The median progression-free survival was 1.8 months and the 6-month and 12-month progression-free survival rates were 30% and 22%, respectively. The median overall survival was 7 months.
“Pembrolizumab demonstrated promising preliminary antitumor activity and a manageable safety profile in this heavily pretreated population of patients with PD-L1–positive advanced squamous cell carcinoma or adenocarcinoma of the esophagus enrolled in KEYNOTE-028,” the researchers wrote. “Evaluation of pembrolizumab for the treatment of esophageal carcinoma is ongoing.”