Abstract 665: Molecular and clinical analyses of patients with gynecologic malignancies treated with PD-1 directed immunotherapy
Authors: Young Kwang Chae, Sabina Murshudova, William H. Bae, Jonathan F. Anker, Mario J. Pineda, Wilberto Nieves-Neira, Daniela E. Matei, John R. Lurain, Shohreh Shahabi, Francis J. Giles
Journal: Cancer Research (2017)

Abstract Long term responses are seldom seen in treatments of advanced or recurrent gynecologic cancers. In contrast, immunotherapeutic strategies targeting immune checkpoints such as programmed cell death-1 (PD-1) are currently in active development in platinum resistant gynecologic malignancies with promising durable responses observed in subset of patients. We analyzed all 14 patients with gynecology malignancies that were treated with PD-1 directed immunotherapy, nivolumab or pembrolizumab at the developmental therapeutics program (DTP) clinic in Northwestern University during 2015 till 2016. Seven patients had ovarian/fallopian/peritoneal cancer; six, endometrial cancer; 1, squamous cell carcinoma (SCC) of cervix that are refractory to standard-of-care chemotherapies. Comprehensive genomic profiling including microsatellite instability (MSI) status and tumor mutational burden (TMB) analyses was performed using next generation sequencing (NGS) (FoundationOne). Among 7 patients with ovarian/fallopian/peritoneal cancer (median age, 62 years), objective response rate (ORR) was 20%. One patient had partial response (PR), another one had stable disease (SD), and 3, progressive disease (PD). Two patients were uable to be evaluated. In a patient with PR, CA 125 level normalized from 426.2 to 10.8 U/mL. Her tumor had very low TMB (1/Mbp). In all patients, TMB level varied from very low to low (1-5 mut/Mbp) with MSI status being stable. Progression free survival (PFS) ranged from 14 to 196 days; overall survival (OS) varied from 60 to 199 days. Among 6 patients with endometrial cancer (median age, 68 years), ORR was 20%. One patient had PR while four experienced PD. One patient whose disease could not be assessed due to early death from an event unrelated to treatment had a remarkable chemical response with a decrease in CA125 level from 5,889 to 182.1 U/mL after one single dose. Her tumor had MSI-stable status and intermediate TMB (6 mut/Mbp). In a patient with PR, CA125 level decreased from 1,216 to 226.5 U/mL. Her tumor had MSI-high status with unknown TMB. Of note, one of four patients with PD had MSI-high status and intermediate level of TMB. Other patients had tumor with MSI-stable status and low level of TMB (3-4 mut/MB). PFS ranged from 23 to 258 days; OS varied from 73 to 265 days. One patient with HPV positive SCC of cervix (34 year old) experienced PD. Her tumor had MSI-stable status with unknown TMB. PFS was 88 days; OS, 132 days. In summary, patients with ovarian and endometrial cancer treated with PD-1 directed immunotherapy demonstrated ORR of 20%. One additional patient with endometrial cancer had an exceptional chemical response. None of the tumors had high TMB (&amp;gt;6/Mbp). No clear associations between genomic traits including TMB and MSI staus and responses were found. Further larger prospecitve studies are warranted to explore potential biomarkers for response with immunotherapy in gynecologic malignancies. Note: This abstract was not presented at the meeting. Citation Format: Young Kwang Chae, Sabina Murshudova, William H. Bae, Jonathan F. Anker, Mario J. Pineda, Wilberto Nieves-Neira, Daniela E. Matei, John R. Lurain, Shohreh Shahabi, Francis J. Giles. Molecular and clinical analyses of patients with gynecologic malignancies treated with PD-1 directed immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 665. doi:10.1158/1538-7445.AM2017-665