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.