The impact of PARP inhibitors in the whole scenario of Ovarian Cancer management: a Systematic Review and Network Meta-Analysis.

PARP inhibitors network meta-analysis ovarian cancer randomized clinical trials

Journal

Critical reviews in oncology/hematology
ISSN: 1879-0461
Titre abrégé: Crit Rev Oncol Hematol
Pays: Netherlands
ID NLM: 8916049

Informations de publication

Date de publication:
06 Dec 2023
Historique:
received: 20 06 2023
accepted: 04 12 2023
medline: 9 12 2023
pubmed: 9 12 2023
entrez: 8 12 2023
Statut: aheadofprint

Résumé

Carboplatin is still the cornerstone of the first-line treatment in advanced Epithelial Ovarian Cancer (aEOC) management and the clinical response to platinum-derived agents remains the major predictor of long-term outcomes. We aimed to identify the best treatment of the aEOC in terms of efficacy and safety, considering all treatment phases. A systematic literature search has been done to compare all treatments in aEOC population. Randomized trials with available survival and safety data published in the 2011-2022 timeframe were enclosed. Only trials reporting the BRCA or HRD (Homologous Recombination Deficiency) status were considered. A ranking of treatment schedules on the progression-free survival (PFS) endpoint was performed. The random-effect model was used to elaborate and extract data. The Network Meta-Analysis (NMA) by Bayesian model was performed by STATA v17. Data on PFS were extracted in terms of Hazard ratio with relative confidence intervals. This NMA involved 18 trials for a total of 9105 patients. Within 12 treatment groups, we performed 3 different sensitivity analyses including "all comers" Intention to Treat (ITT) population, BRCA-mutated (BRCAm), and HRD subgroups, respectively. Considering the SUCRA-reported cumulative PFS probabilities, we showed that in the ITT population, the inferred best treatment was niraparib plus bevacizumab with a SUCRA of 96.7. In the BRCAm subgroup, the best SUCRA was for olaparib plus chemotherapy (96,9). The HRD population showed an inferred best treatment for niraparib plus bevacizumab (SUCRA 98,4). Moreover, we reported a cumulative summary of PARPi toxicity, in which different 3-4 grade toxicity profiles were observed, despite the PARPi "class effect" in terms of efficacy. Considering all aEOC subgroups, the best therapeutical option was identified as PARPi plus chemotherapy and/or antiangiogenetic agents, suggesting the relevance of combinatory approaches based on molecular profile. This work underlines the potential value of "chemo-free" regimens to prolong the platinum-free interval (PFI).

Sections du résumé

BACKGROUND BACKGROUND
Carboplatin is still the cornerstone of the first-line treatment in advanced Epithelial Ovarian Cancer (aEOC) management and the clinical response to platinum-derived agents remains the major predictor of long-term outcomes.
PATIENT AND METHODS METHODS
We aimed to identify the best treatment of the aEOC in terms of efficacy and safety, considering all treatment phases. A systematic literature search has been done to compare all treatments in aEOC population. Randomized trials with available survival and safety data published in the 2011-2022 timeframe were enclosed. Only trials reporting the BRCA or HRD (Homologous Recombination Deficiency) status were considered.
DATA EXTRACTION AND SYNTHESIS METHODS
A ranking of treatment schedules on the progression-free survival (PFS) endpoint was performed. The random-effect model was used to elaborate and extract data. The Network Meta-Analysis (NMA) by Bayesian model was performed by STATA v17. Data on PFS were extracted in terms of Hazard ratio with relative confidence intervals.
RESULTS RESULTS
This NMA involved 18 trials for a total of 9105 patients. Within 12 treatment groups, we performed 3 different sensitivity analyses including "all comers" Intention to Treat (ITT) population, BRCA-mutated (BRCAm), and HRD subgroups, respectively. Considering the SUCRA-reported cumulative PFS probabilities, we showed that in the ITT population, the inferred best treatment was niraparib plus bevacizumab with a SUCRA of 96.7. In the BRCAm subgroup, the best SUCRA was for olaparib plus chemotherapy (96,9). The HRD population showed an inferred best treatment for niraparib plus bevacizumab (SUCRA 98,4). Moreover, we reported a cumulative summary of PARPi toxicity, in which different 3-4 grade toxicity profiles were observed, despite the PARPi "class effect" in terms of efficacy.
CONCLUSIONS CONCLUSIONS
Considering all aEOC subgroups, the best therapeutical option was identified as PARPi plus chemotherapy and/or antiangiogenetic agents, suggesting the relevance of combinatory approaches based on molecular profile. This work underlines the potential value of "chemo-free" regimens to prolong the platinum-free interval (PFI).

Identifiants

DOI: 10.1016/j.critrevonc.2023.104229 PMID: 38065404
pubmed: 38065404
pii: S1040-8428(23)00317-7
doi: 10.1016/j.critrevonc.2023.104229
pii:
doi:

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

104229

Informations de copyright

Copyright © 2023. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Conflicts of interest All authors declare that they have no conflicts of interest.

Auteurs

Nicoletta Staropoli (N)

Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy; Medical and Translational Oncology Unit, AOU Renato Dulbecco, Catanzaro, Italy.

Domenico Ciliberto (D)

Medical and Translational Oncology Unit, AOU Renato Dulbecco, Catanzaro, Italy.

Francesco Luciano (F)

Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy.

Cristina Napoli (C)

Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy.

Martina Costa (M)

Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy.

Giacomo Rossini (G)

Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy.

Mariamena Arbitrio (M)

Institute for Biomedical Research and Innovation (IRIB), National Research Council of Italy (CNR), Catanzaro, Italy.

Caterina Labanca (C)

Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy.

Caterina Riillo (C)

Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy.

Teresa Del Giudice (T)

Oncology Unit, "De Lellis" Facility, AOU Renato Dulbecco Catanzaro.

Antonella Crispino (A)

Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy.

Angela Salvino (A)

Medical and Translational Oncology Unit, AOU Renato Dulbecco, Catanzaro, Italy.

Antonio Galvano (A)

Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, 90127 Palermo, Italy.

Antonio Russo (A)

Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, 90127 Palermo, Italy; S.H.R.O., Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, US.

Pierfrancesco Tassone (P)

Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy; Medical and Translational Oncology Unit, AOU Renato Dulbecco, Catanzaro, Italy; S.H.R.O., Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, US.

Pierosandro Tagliaferri (P)

Department of Experimental and Clinical Medicine, Magna Græcia University, Catanzaro, Italy; Medical and Translational Oncology Unit, AOU Renato Dulbecco, Catanzaro, Italy. Electronic address: tagliaferri@unicz.it.

Classifications MeSH