Pembrolizumab in advanced endometrial cancer: Preliminary results from the phase Ib KEYNOTE-028 study.

Abstract

5581 Background: There are currently no treatment options for pts with endometrial cancer who progress on chemotherapy. Pembrolizumab is an anti–PD-1 antibody that blocks interaction between PD-1 and its ligands, PD-L1/PD-L2. The safety and efficacy of pembrolizumab were evaluated in advanced solid tumors in the KEYNOTE-028 study (NCT02054806). Preliminary results from the endometrial carcinoma cohort are presented. Methods: Key inclusion criteria were advanced endometrial carcinoma (excluded sarcomas, mesenchymal tumors), failure of prior systemic therapy, ECOG PS 0-1, and PD-L1 expression in ≥ 1% of tumor or stroma cells by IHC. Pembrolizumab 10 mg/kg every 2 wk was given for up to 24 mo or until confirmed progression, intolerable toxicity, death, or consent withdrawal. Response was assessed every 8 wk for the first 6 mo and every 12 wk thereafter. The primary end point was ORR per RECIST v1.1 by investigator assessment. Results: In the 24 pts enrolled, median age was 67.0 y; 66.7% had an ECOG PS of 1; 62.4% received ≥ 2 prior therapies for metastatic disease. As of Dec 10, 2015, median follow-up duration was 69.9 wk (range, 5.4-84.4). Treatment-related AEs (TRAEs) occurred in 13 (54.2%) pts; most common were pruritus (n = 4, 16.7%), asthenia, fatigue, pyrexia, and decreased appetite (n = 3 each; 12.5%). Three pts experienced grade 3 TRAEs: 1 pt had back pain and asthenia (both resolved), 1 pt had diarrhea (resolved), 1 pt had asthenia, anemia, hyperglycemia, and hyponatremia (all unresolved). No pts died or discontinued pembrolizumab because of a TRAE. ORR (confirmed) was 13.0% (PR, n = 3; 95% CI, 2.8-33.6); median duration of response was not yet reached (range, 40.3+ to 65.1+ wk). Three pts achieved stable disease (13%; 95% CI, 2.8-33.6; median duration, 24.6 wk [range, 13.1-24.6]). Six-mo PFS and OS rates were 19.0% and 68.8%, respectively. At data cutoff, all 3 pts with PRs remained on treatment. Conclusions: Pembrolizumab demonstrated an acceptable safety profile and preliminary antitumor activity in heavily pretreated PD-L1+ advanced endometrial cancer pts. The clinical benefit of pembrolizumab for advanced endometrial cancer is being further investigated in the phase 2 KEYNOTE-158 trial (NCT02628067). Clinical trial information: NCT02054806.