Autori
L. Gasperoni, L. Cancanelli, A. Ossato, L. Del Bono, S. Vecchia, C. Fontanella, V. Damuzzo, A. Messori

Rivista
Cancers

Topic

Analisi statistiche e metanalisi

Impact Factor
5,2

Abstract

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.

 

Link PubMed del paper
https://www.mdpi.com/2072-6694/17/22/3714