Sensitivity of Platinum-Based Chemotherapy and Efficacy of Arsenic Trioxide-Based Non-Platinum Chemotherapy Following the Progression of PARPi Maintenance Therapy: A Real-World Study

Abstract

Background

Cross-resistance is observed between platinum and Poly (ADP-ribose) polymerase inhibitors (PARPi). We aim to propose the definition of PARPi resistance and demonstrate the best therapeutic strategy for patients with PARPi resistance.

Methods

A retrospective analysis was performed on patients diagnosed with epithelial ovarian cancer from October 2015 to November 2022. Patients were treated with PARPi for more than 6 months and received chemotherapy after progression.

Results

Totally, 41 patients were enrolled, with 21 receiving PARPi for 6 to 12 months and 20 for more than 12 months. The median duration of PARPi was 12 months, and the median time to second progression (TTSP) was 3.45 months (range, 1.0–20.2 months). The Kaplan–Meier and Cox analysis revealed a significantly shorter TTSP for patients who received PARPi for more than 12 months compared to those for 6 to 12 months. After PARPi resistance, 34 (82.9%) received platinum-based chemotherapy, with an overall response rate (ORR) of 26.5% (9/34). Seven patients (17.1%) received arsenic trioxide (ATO)-based chemotherapy, with an ORR of 57.1% (4/7). During subsequent chemotherapy, 12/34 patients switched to ATO-based chemotherapy due to progression, of which five cases were evaluated as effective (41.7%).

Conclusion

PARPi resistance has a negative impact on the subsequent chemotherapy. The progression of the disease beyond 6 to 12 months should be considered as acquired resistance. Non-platinum chemotherapy, such as ATO-based combined sequential chemotherapy, may emerge as the preferred option for patients with PARPi resistance.