Updated results for the advanced esophageal carcinoma cohort of the phase 1b KEYNOTE-028 study of pembrolizumab.

Abstract

4046 Background: PD-L1 expression is associated with poor prognosis in esophageal cancer. Pembrolizumab (pembro) is a monoclonal antibody against PD-1 that helps to restore antitumor immune surveillance. The multicohort, phase 1b KEYNOTE-028 (NCT02054806) trial was designed to evaluate the safety and efficacy of pembro in patients with PD-L1+ advanced solid tumors. Updated results from the esophageal carcinoma cohort of KEYNOTE-028 are reported. Methods: Key eligibility criteria included advanced PD-L1+ squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction, failure of standard therapy, and ECOG PS 0-1. Patients received pembro 10 mg/kg every 2 wk for up to 2 y or until confirmed progression, intolerable toxicity, or investigator decision. Response was assessed every 8 wk for the first 6 mo and every 12 wk thereafter. Primary end point was ORR per RECIST v1.1 by investigator review. Results: In the 23 patients enrolled, median age was 65 y, 83% were men, 74% had squamous histology, and 87% received ≥ 2 prior therapies for metastatic disease. As of the Nov 4, 2015, data cutoff date, median follow-up duration was 7.1 mo (range, 1.3-19.4 mo). 9 patients (39%) had treatment-related adverse events (AEs), most commonly decreased appetite (n = 3, 13%). 4 (17%) patients experienced grade 3 treatment-related AEs (decreased lymphocytes in 2 patients and decreased appetite, liver disorder, and pruritic rash in 1 patient each). There were no treatment-related deaths or discontinuations. Immune-mediated AEs included grade 2 hypothyroidism in 2 patients (9%) and adrenal insufficiency and pruritic rash in 1 patient (4%) each. ORR was 30% (95% CI, 13%-53%), and the stable disease rate was 9% (95% CI, 1%-28%). 4 of 7 responses were ongoing at data cutoff, with a median duration of response not reached (range, 5.5-11.8+ mo). Conclusions: After additional follow-up, pembro continued to show manageable toxicity and durable antitumor activity in patients with heavily pretreated, PD-L1+ advanced esophageal carcinoma. Phase 2 and 3 trials of pembro in patients with esophageal carcinoma are ongoing. Clinical trial information: NCT02054806.