Tumor molecular profiling of responders and non-responders following pembrolizumab monotherapy in chemotherapy resistant advanced cervical cancer

Publication date: May 2018Source: Gynecologic Oncology Reports, Volume 24Author(s): N.Y.L. Ngoi, V. Heong, X.W. Lee, Y.Q. Huang, Y.L. Thian, B.A. Choo, D. Lim, Y.W. Lim, S.E. Lim, A. Ilancheran, R. Soong, D.S.P. TanAbstractOptimal treatment for advanced cervical cancer after first line chemotherapy remains undefined. Immune checkpoint inhibition with pembrolizumab, a programmed cell death protein 1(PD-1) inhibitor, is under investigation. We analyzed the micro-environmental and molecular genetic profile of tumors from 4 patients with metastatic cervical cancer treated with off-label second-line pembrolizumab in an effort to identify predictive biomarkers. All patients received 2 mg/kg of pembrolizumab, 3-weekly until disease progression. Immunohistochemistry(IHC) for PD-1, PD-L1, CD3 and CD8, as well as next generation sequencing (NGS) for 50 cancer-related genes were performed on tumor samples. All patients tolerated treatment well with no discontinuation of treatment due to toxicity. One patient experienced dramatic and prolonged partial response, and remains stable on pembrolizumab with a progression free survival (PFS) of 21 months at the time of reporting of this series. Three patients experienced disease progression as best response. In the exceptional responder, there was no tumoral expression of PD-L1, however, combined positive score (CPS) for PD-L1 was 1 and we identified somatic mutations in ERBB4(R612W), PIK3CA(E542K) and RB1(E365K). In 2 patients, despite pro...
Source: Gynecologic Oncology Reports - Category: OBGYN Source Type: research