16IN - Combining PARP inhibitors with CPI

Date 06 March 2018
Event TAT 2018 - Targeted Anticancer Therapies
Session Combining immune therapy and targeted therapies
Topics Cancer Immunology and Immunotherapy
Presenter Filipa Lynce
Citation Annals of Oncology (2018) 29 (suppl_3): iii1-iii6. 10.1093/annonc/mdy046
Authors F. Lynce
  • Georgetown University, 20057 - Washington/US

Abstract

Immunotherapy has shifted the treatment paradigm for many malignancies, but not all cancer types have enjoyed a clinically meaningful response from checkpoint blockade. Therefore combination therapies that allow enhancement of the antitumor immune response are needed. Poly(ADP-ribose) polymerase (PARP) inhibitors may stimulate antigen presentation via increased T cell cytotoxic activity. In preclinical models, the combination of PARP inhibition with anti-PD-L1 therapy compared with each agent alone has been shown to significantly increase the therapeutic efficacy. PARP inhibitors when combined with anti-CTLA-4 therapy in BRCA1-deficient ovarian tumor models have also been found in vitro to induce long-term survival. One group that may benefit from this approach are tumors with germline or somatic mutations in the homologous recombination (HR) DNA damage repair pathway – including BRCA1/2, PALB2, ATM, and the FANC family of genes among others. It is unclear whether this benefit can be extended to HR proficient tumors. This presentation overviews these data and ongoing clinical trials designed to answer these questions.