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.

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.