Association Between Prior PARP Inhibitor Maintenance Therapy and Myelosuppression During Subsequent Chemotherapy in Ovarian Cancer

Abstract

Background:

Poly (ADP-ribose) polymerase inhibitors (PARPis) are commonly used as maintenance therapy following first-line chemotherapy for ovarian cancer and are associated with myelosuppression during treatment. However, there is limited guidance on the potential impact of prior PARPi exposure on the tolerance of subsequent chemotherapy.

Objective:

The purpose of this study was to evaluate the association between prior PARPi maintenance therapy and myelosuppression during second-line chemotherapy for ovarian cancer.

Methods:

A retrospective, single-center, cohort study was conducted of adult women with ovarian cancer who received second-line chemotherapy between January 2017 and June 2024 at a community-teaching hospital. Patients receiving PARPi maintenance following first-line therapy were compared with those who did not receive maintenance. The primary outcome was neutropenia (absolute neutrophil count [ANC] <1500 cells/µL) during second-line chemotherapy. Secondary outcomes included severe neutropenia, anemia, thrombocytopenia, chemotherapy delay, and use of granulocyte colony-stimulating factors (G-CSFs) during second-line chemotherapy.

Results:

Forty-two patients were included; 11 received prior PARPi maintenance and 31 did not. Neutropenia occurred more frequently in the PARPi-exposed group compared with the non-PARPi group (91% vs 52%, odds ratio [OR] = 9.35, 95% CI = 1.07-83.3, P = .030), with effect estimates remaining large and directionally consistent on multivariable analysis adjusting for baseline ANC (OR = 6.36) and propensity score (OR = 6.10). Median nadir ANC was significantly lower with the PARPi-exposed group (1004 vs 1380 cells/µL, P = .019), and secondary G‑CSF prophylaxis was more frequently utilized (73% vs 23%, P = .008). No patients received erythropoiesis-stimulating agents. Limitations included the retrospective design, small sample size, single-center setting, and heterogeneity in second-line chemotherapy regimens.

Conclusion and Relevance:

This exploratory, hypothesis-generating study suggests prior PARPi maintenance may increase the risk of neutropenia and the need for G-CSF use during subsequent chemotherapy. These findings highlight the need for heightened monitoring and supportive care consideration in this population and warrant validation in larger studies.