Platinum-Based Chemotherapy Following Progression on PARP Inhibitor Maintenance Yields Greatest Benefit in Advanced Ovarian Cancer with Platinum-Free Interval >12 Months

Web Exclusives - Ovarian Cancer

Real-world data confirm that the benefit of platinum-based chemotherapy in patients with high-grade serous ovarian cancer whose disease progresses following poly (ADP-ribose) polymerase (PARP) inhibitor treatment is greatest in those patients with a platinum-free interval >12 months.

In an analysis of 54 patients with high-grade serous ovarian cancer who were treated with chemotherapy after progressing on maintenance PARP inhibitors, median overall survival (OS) was 6.8 months for patients who received subsequent nonplatinum chemotherapy, 14.2 months for patients who received PARP maintenance with a platinum-free interval of 6 to 12 months, and 28.2 months for those who received PARP maintenance with a platinum-free interval >12 months. The data were presented by Andrea Plaja Salarich, MD, Medical Oncology Department, Catalan Institute of Oncology, Badalona, Spain, and colleagues at the European Society for Medical Oncology Virtual Congress 2020.

PARP inhibitors and platinum therapies have similar mechanisms of action, and cross-resistance has been demonstrated, casting doubt on the benefit of subsequent platinum therapy after PARP inhibitor progression. The investigators sought real-world data to examine platinum outcomes after PARP inhibition.

The 54 patients included in the analysis were treated with subsequent chemotherapy after progression following maintenance with PARP inhibitors at 3 hospitals. Slightly more than half (57.4%) of patients had BRCA-mutated cancer. Overall, 4 (7.4%) received PARP inhibitors after first-line therapy, 25 (46.3%) received PARP inhibitors after second-line therapy, and 25 (46.3%) received PARP inhibitors after third (or subsequent)-line therapy. Thirty-four (63%) patients received olaparib (Lynparza) as their PARP inhibitor and 20 (37%) received niraparib (Zejula). Median progression-free survival (PFS) with the use of PARP inhibitors as maintenance in the recurrent setting was 7.5 months, and PFS to subsequent chemotherapy was 15.4 months.

Median PFS was 5.1 months, 5.1 months, and 9.4 months for patients who received subsequent nonplatinum chemotherapy, patients with a platinum-free interval of 6 to 12 months, and those with a platinum-free interval >12 months, respectively.

The overall response rate associated with subsequent platinum therapy was 33.3% and disease progression was 28.6%.

For patients with a platinum-free interval of 6 to 12 months, 22.7% had a partial response, 27.3% had stable disease as their best response, and 50.0% had progressive disease.

For patients with a platinum-free interval >12 months, 20% had a complete response and 25% had a partial response, 50% had stable disease, and 5% had progressive disease. The 4 patients who experienced complete response had BRCA-mutation–positive tumors and were receiving PARP inhibitors in the recurrent setting.

For the patients who received subsequent nonplatinum chemotherapy, 28.6% achieved partial response, 28.6% had stable disease, and 42.9% experienced disease progression.

Median PFS was 5.1 months, 5.1 months, and 9.4 months for patients who received subsequent nonplatinum chemotherapy, patients with a platinum-free interval of 6 to 12 months, and those with a platinum-free interval >12 months, respectively (P = .055 for platinum vs nonplatinum chemotherapy comparison). A similar trend was observed for median OS, which was 6.8 months, 14.2 months, and 28.2 months, among the 3 patient groups, respectively (P = .018 for platinum vs nonplatinum chemotherapy comparison).

The investigators concluded that the role of subsequent platinum after PARP inhibitor therapy in the subgroup with a 6- to 12-month platinum-free interval warrants further research.

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Last modified: November 19, 2020