Dr. Konstantinopoulos Discusses PARP Plus Immunotherapy

Panagiotis A. Konstantinopoulos, MD, PhD, director, Translational Research, Gynecologic Oncology, Dana-Farber Cancer Institute, associate professor of medicine, Harvard Medical School, discusses the combination of PARP inhibitors and immunotherapy.

Konstantinopoulos explains that PARP inhibitors can induce double-strand breaks, which can lead to activation of the immune system either through increased neoantigens or activation of the STING pathway. The STING pathway is involved in innate immunity, he adds. Additionally, PARP inhibitors can also upregulate PD-L1 through the activation of a double-strand break in ATM- and ATR-Chk1.

Immune activation as a result of PARP inhibition paired with PD-L1 overexpression provides necessary immune priming for the cancer cells to respond to immunotherapy, according to Konstantinopoulos. This was the preclinical evidence for the phase I/II TOPACIO/KEYNOTE-162 study (NCT02657889), which is evaluating the combination of the PARP inhibitor niraparib (Zejula) and the PD-1 inhibitor pembrolizumab (Keytruda) in patients with recurrent ovarian cancer.