# Comparative Analysis of Maintenance Treatments in Patients with Newly Diagnosed Advanced Ovarian Cancer After First-Line Platinum-Based Regimens

## TL;DR

This study compares different maintenance treatments for advanced ovarian cancer, finding that olaparib-based regimens work best in patients with specific genetic markers.

## Contribution

The study provides the first indirect comparison of PARPi regimens using reconstructed patient data from multiple trials, highlighting treatment efficacy based on BRCA and HRD status.

## Key findings

- Olaparib plus bevacizumab showed the best progression-free survival in BRCA+ patients.
- PARPi provided limited benefit in HRD-negative patients compared to bevacizumab alone.
- Niraparib had higher rates of severe hematologic adverse events compared to olaparib.

## Abstract

Poly (ADP-ribose) polymerase inhibitors (PARPi) are standard first-line maintenance therapy in advanced ovarian cancer, but their benefit is strongly influenced by BRCA status and homologous recombination deficiency (HRD), and no direct head-to-head trials exist. We performed an indirect comparison using reconstructed individual patient data from Kaplan–Meier curves of phase III studies (SOLO1, PRIMA, PAOLA1, ATHENA, FLAMES). The primary endpoint was progression-free survival (PFS), while overall survival (OS) was exploratory. Subgroups were BRCA−mutated (BRCA+), BRCA−/HRD+, and BRCA−/HRD−. Safety was assessed through a network meta-analysis of adverse events. In BRCA+ patients, the largest PFS benefit was observed with olaparib plus bevacizumab, followed by olaparib monotherapy, while niraparib performed worse. In BRCA−/HRD+ disease, olaparib plus bevacizumab outperformed niraparib and rucaparib, with restricted mean survival time gains of 3–4 months. In BRCA−/HRD− patients, PARPi yielded only modest benefits, showing no advantage over bevacizumab alone. Exploratory OS analysis confirmed durable survival with olaparib in BRCA+ but not in other subgroups. Regarding safety, olaparib demonstrated the most favorable hematologic profile, whereas niraparib was linked to higher rates of severe anemia, thrombocytopenia, and neutropenia, although it showed lower gastrointestinal toxicity and fatigue. In conclusion, PARPi efficacy is highly dependent on BRCA and HRD status: olaparib-based regimens provide the greatest clinical advantage with manageable safety in BRCA+ and HRD+ disease, while their value in HRD-negative ovarian cancer remains limited.

Background: Poly (ADP-ribose) polymerase inhibitors (PARPi) are the standard of care for first-line maintenance in advanced ovarian cancer, but their benefit varies by BRCA and homologous recombination deficiency (HRD) status, and no head-to-head comparisons are available. Methods: We conducted an indirect comparison of PARPi regimens using reconstructed individual patient data (IPD) from Kaplan–Meier curves of phase III randomized trials (SOLO1, PRIMA, PAOLA1, ATHENA, FLAMES). Progression-free survival (PFS) was the primary endpoint; overall survival (OS) was exploratory. Subgroups were defined as BRCA−mutated (BRCA+), BRCA−/HRD+, and BRCA−/HRD−. Safety outcomes were assessed through a network meta-analysis of adverse drug reactions (ADRs). Results: In BRCA+ patients, olaparib + bevacizumab achieved the largest PFS improvement (HR = 0.27; 95%CI: 0.19–0.39), followed by olaparib monotherapy, while niraparib performed significantly worse. In BRCA−/HRD+, olaparib + bevacizumab was superior to niraparib and rucaparib, with restricted mean survival time (RMST) gains of 3–4 months. In BRCA−/HRD−, PARPi produced only a modest benefit, with no advantage over bevacizumab monotherapy. Exploratory OS analysis confirmed long-term survival with olaparib in BRCA+ but not in the other subgroups. Safety analysis indicated olaparib had the most favorable hematological profile, while niraparib was associated with the highest rates of severe anemia, thrombocytopenia, and neutropenia, despite showing lower gastrointestinal toxicity and fatigue incidence. Conclusions: PARPi efficacy depends strongly on BRCA and HRD status. Olaparib-based regimens provide the greatest clinical benefit with acceptable safety in BRCA+ and HRD+ disease, whereas PARPi appear to be of limited value in HRD-negative ovarian cancer.