Pattern of disease in recurrent cervical cancer associated with response to pembrolizumab.

Abstract

e18006 Background: Pembrolizumab received accelerated FDA approval for treatment of metastatic or recurrent PD-L1 positive cervical cancer in 6/2018. Since then, the clinical characteristics of patients who best respond to this immunotherapy have remained undefined. We sought to describe patients with advanced cervical cancer who derived durable clinical benefit (DCB) from pembrolizumab therapy. Methods: Patients with advanced or recurrent cervical cancer who received pembrolizumab from 8/2017-12/2019 at our institution were assessed. Reviewed data included patient demographics, treatment history, baseline pattern of metastatic disease at initiation of anti-PD-1 treatment, and outcomes. Kaplan-Meier survival analysis was performed to determine progression-free survival (PFS). Treatment response was evaluated by computed tomography using RECIST 1.1 criteria. Results: 14 patients with recurrent cervical cancer received pembrolizumab. Median age was 55 years (range, 21-76); 79% (n = 11) had squamous cell carcinoma (SCC). The 3 non-SCC histologies included endocervical adenocarcinoma, high-grade endometroid adenocarcinoma, and mesonephric adenocarcinoma. 93% (n = 13) expressed PD-L1; 1 patient whose tumor was MSI-H did not undergo PD-L1 testing. 93% (n = 13) had received prior radiation, and 86% (n = 12) had received 1 or more prior lines of chemotherapy. Median duration of treatment was 4.9 months (range, 1.4-15.2), and median follow-up was 7.9 months (range, 2.1-29.9). On RECIST review, the overall response rate was 21% (n = 3), including 2 partial responses and 1 complete response. Two patients (14%) had stable disease of ≥6 months for an observed DCB of 36%. Of the 5 patients with DCB, 4 remain on pembrolizumab, with observed antitumor activity of up to 15.4 months. On univariable analysis, a lymph node and/or lung only baseline pattern of metastasis was associated with improved response to pembrolizumab (n = 7, P= 0.02). On survival analysis, patients with lymph node and/or lung pattern of disease had a 6-month PFS rate of 86%, compared to a 6-month PFS rate of 0% in patients with visceral or multi-site disease ( P< 0.001). Conclusions: Pembrolizumab showed promising activity in our patient cohort, with a DCB rate of 33%. Patients with lymph node and/or lung only patterns of metastasis at baseline had the greatest radiologic response compared to patients with visceral or multi-site disease. Our results suggest that there may be an underlying pathophysiology of metastatic patterns that confer improved response to anti-PD-1 therapy in advanced cervical cancer.