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A Network Meta-Analysis Comparing Efficacy of First-Line Maintenance PARP Inhibitors

Conference Correspondent  - ESMO Highlights

For most women newly diagnosed with advanced ovarian cancer, surgical resection and adjuvant platinum-based chemotherapy will not prevent relapse within 3 years. As such, poly (ADP-ribose) polymerase (PARP) inhibitors and antiangiogenic agents have been studied as maintenance therapies for these patients, but results have varied. This network analysis was conducted to examine the relative efficacy of first-line maintenance PARP inhibitors to one another when treating women with advanced ovarian cancer.

In addition, relative efficacy of PARP inhibitors versus first-line antiangiogenic agents was also compared. For a study to be included in the analysis, it had to be published in English; include patients with a diagnosis of advanced ovarian cancer; include treatment with the PARP inhibitors olaparib, niraparib, or veliparib, or the antiangiogenic agents bevacizumab, pazopanib, or nintedanib; and be a phase 3 randomized study reporting on progression, death, and adverse events.

Seven studies with a total of 7700 patients were included in the meta-analysis. The relative risk of death and progression was highest with control and bevacizumab, which were followed by nintedanib, pazopanib, veliparib, niraparib, and olaparib, in that order. The relative risk of adverse events grade ≥3 was highest with pazopanib, followed by nirapanib, olaparib, nintedanib, bevacizumab, veliparib, and control, in that order.

For several subgroups, treatment with a PARP inhibitor significantly improved progression-free survival. These groups included those with homologous recombination deficiency (HRD+), HRD–, BRCA mutation (BRCA+), BRCA–, BRCA2+, stage III, and stage IV. In BRCA+ patients, PARP inhibitors demonstrated similar reduction in relative risk of death and progression. For HRD+ patients, olaparib had the lowest relative risk of death and progression, followed by niraparib, veliparib, and control, in that order. This was not the same for HRD–. For these patients, relative risk of death and progression was lowest with veliparib followed by niraparib, then olaparib, which was similar to control.

For advanced ovarian cancer, this study is the first network meta-analysis to compare and rank first-line maintenance treatment therapies. In general, it reveals that PARP inhibitors are associated with better outcomes than antiangiogenic agents. Across mutation subtypes, the frequency of adverse events grade ≥3 varies by individual PARP inhibitor, as does clinical efficacy.

Reference

Abstract and Poster 826P. ESMO 2020. September 19-21, 2020. Comparative efficacy of first-line maintenance PARP inhibitors (PARPI) in advanced ovarian cancer (OC): a network meta-analysis.

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