Background
Ovarian cancer is a common malignant tumor of female reproductive system and its mortality ranks first among gynecological malignant tumors1. Although surgical techniques have improved and the vast majority of patients are sensitive to paclitaxel combined with platinum-based chemotherapy, more than 75% of patients eventually relapse within two years of initial treatment2. Patients with platinum-sensitive relapse are recommended re-challenge with platinum-based chemotherapy until platinum resistance, however, once platinum resistance occurs, the response rate of subsequent chemotherapy is only about 10-25%, and the prognosis is extremely poor, with median survival of only 12 months2, 3.
Breast cancer susceptibility genes (BRCA) participate in the repair of DNA double-strand breaks through homologous recombination (HR). BRCA1/2 mutant ovarian cancer cells have impaired repair of DNA double-strand breaks, so the DNA repair pathway relies on poly (ADP-Ribose) polymerase (PARP) to mediate repair of DNA single-strand breaks to maintain DNA survival4. Therefore, PARP inhibitors can block the repair of DNA damage in BRCA mutant cells and lead to cell apoptosis, which is known as the ”synthetic lethal” effect4. Conventional platinum-based therapy follows a frequent relapse-response pattern, so subsequent chemotherapy response and prognosis can be predicted based on the patient’s platinum-free interval5, however, the regimen of PARPi is different and continuous treatment is recommended until disease progression6, 7, so the concept of PFI has become controversial. The sensitivity of platinum drugs is highly consistent with the response of PARPi, as both are closely related to alterations in DNA damage repair, which also leads to significant overlap between platinum and PARPi resistance mechanisms8.
Several PARPi are currently available for the clinical treatment of patients with ovarian cancer, and can significantly improve PFS6, 9, however, there was no relevant study on whether PARPi monotherapy was more beneficial compared with platinum-based chemotherapy. Besides, several clinical data suggested that prolonging the PFI (using non-platinum-based regimens) might restore platinum sensitivity and thus improved survival10, 11, thus, as a non-platinum-based treatment regimen, PARPi monotherapy after relapse could prolong the PFI, but it was unknown whether platinum-based chemotherapy was more effective after PARPi resistance, and whether it could prolong the survival of patients. Therefore, we conducted this retrospective analysis to try to address this clinically urgent question.