Loss-of-function mutations in PPP2R1A Correlate with Exceptional Survival in Ovarian Clear Cell Carcinomas Treated with Immune Checkpoint Inhibitors (099)

Abstract

Objectives: Response rates to immune checkpoint inhibitors (ICI) in recurrent ovarian cancer have been disappointingly low. While emerging data suggest increased activity in patients with ovarian clear cell carcinomas (OCCC), only a minority of patients benefit even among this group. The objective of the current study was to investigate correlates of long-term survival in patients with OCCC treated with ICI. Methods: A review of medical records identified 28 patients with ovarian/peritoneal clear cell carcinoma who had been treated with CTLA4 and PD1/L1 ICI immunotherapy as part of two prospective RCTs. All patients except one received tremelimumab and durvalumab, either sequentially or in combination, and one additional patient received ipilimumab and nivolumab. Clinical-pathologic and tumor somatic mutation information (obtained from clinical next-generation sequencing) were correlated with overall survival (OS) using Kaplan-Meier and log-rank methodologies. Conclusions: These preliminary data suggest that PPP2R1A (rather than ARID1A) mutations may serve as a biomarker for long-term survival after ICI in OCCC, and ongoing research is aimed at determining a causal relationship. Given the benefit was delayed and often followed initial progression, harboring PPP2R1A mutations on ICI treatment beyond progression in patients with OCCC may be a consideration after appropriate counseling. Objectives: Response rates to immune checkpoint inhibitors (ICI) in recurrent ovarian cancer have been disappointingly low. While emerging data suggest increased activity in patients with ovarian clear cell carcinomas (OCCC), only a minority of patients benefit even among this group. The objective of the current study was to investigate correlates of long-term survival in patients with OCCC treated with ICI. Methods: A review of medical records identified 28 patients with ovarian/peritoneal clear cell carcinoma who had been treated with CTLA4 and PD1/L1 ICI immunotherapy as part of two prospective RCTs. All patients except one received tremelimumab and durvalumab, either sequentially or in combination, and one additional patient received ipilimumab and nivolumab. Clinical-pathologic and tumor somatic mutation information (obtained from clinical next-generation sequencing) were correlated with overall survival (OS) using Kaplan-Meier and log-rank methodologies. Conclusions: These preliminary data suggest that PPP2R1A (rather than ARID1A) mutations may serve as a biomarker for long-term survival after ICI in OCCC, and ongoing research is aimed at determining a causal relationship. Given the benefit was delayed and often followed initial progression, harboring PPP2R1A mutations on ICI treatment beyond progression in patients with OCCC may be a consideration after appropriate counseling.