Federica Tomao1, Erlisa Bardhi2, Anna Di Pinto1, Carolina Maria Sassu1, Elena Biagioli3, Maria Cristina Petrella4, Innocenza Palaia1, Ludovico Muzii1, Nicoletta Colombo5, Pierluigi Benedetti Panici1. 1. Department of Maternal and Child Health and Urological Sciences, "Sapienza" University of Rome, Policlinico Umberto I, Viale del Policlinico 155, 00161 Rome, Italy. 2. Department of Maternal and Child Health and Urological Sciences, "Sapienza" University of Rome, Policlinico Umberto I, Viale del Policlinico 155, 00161 Rome, Italy. Electronic address: erlibardhi@gmail.com. 3. Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milano, Italy. 4. AOUC Azienda Ospedaliero-Universitaria Careggi, Reparto di Oncologia Medica, Largo G. Alessandro Brambilla, 3, 50134 Firenze FI, Italy. 5. Istituto Europeo di Oncologia, Corso di PortaVittoria, 49, 20122 Milano, Italy.
Abstract
OBJECTIVE: This meta-analysis investigated the effectiveness of PARP inhibitors (PARPis) as maintenance treatment in platinum sensitive recurrent ovarian cancer (ROC), stratifying results based on BRCA mutational status into five different categories: whole population, germ-line BRCA mutated patients, somatic BRCA mutated patients, HRD patients and wild type population. METHODS: PubMed, Medline, Scopus, EMBASE and clinicaltrials.gov, as well as meeting proceedings were searched for eligible studies that described RCTs testing the efficacy of PARPis as maintenance treatment in platinum sensitive ROC. Data were extracted independently and analysed using RevMan statistical software version 5.3. Primary end-point was progression free survival (PFS). RESULTS: The analysis confirmed the positive effect of PARPis in patients with platinum sensitive ROC in case of germinal or somatic BRCA mutations. Specifically, HR for PFS was 0.26, 95% CI 0.21-0.31, p < 0.00001 for the mutation of BRCA gene and 0.24, 95%, CI 0.12-0.48, p < 0.0001 for the somatic alteration. In addition, in the HRD population, studies that analysed the efficacy of PARPis reported a PFS improvement with HR 0.34, 95% CI 0.26-0.43, p < 0.00001. Finally, our analysis confirms the role of these drugs in prolonging PFS in the whole population with HR 0.36, 95% CI 0.32-0.42, p < 0.00001, although to a lesser extent, with a significant improvement even in wild type cancers with HR 0.49, 95%, CI 0.41-0.59, p < 0.00001). CONCLUSIONS: PARPis are effective regardless of BRCA mutational status. Future investigations are necessary to explore the use of different PARPis as monotherapy, comparing them among each other in terms of efficacy and toxicity, and exploring their potential re-use.
OBJECTIVE: This meta-analysis investigated the effectiveness of PARP inhibitors (PARPis) as maintenance treatment in platinum sensitive recurrent ovarian cancer (ROC), stratifying results based on BRCA mutational status into five different categories: whole population, germ-line BRCA mutated patients, somatic BRCA mutated patients, HRDpatients and wild type population. METHODS: PubMed, Medline, Scopus, EMBASE and clinicaltrials.gov, as well as meeting proceedings were searched for eligible studies that described RCTs testing the efficacy of PARPis as maintenance treatment in platinum sensitive ROC. Data were extracted independently and analysed using RevMan statistical software version 5.3. Primary end-point was progression free survival (PFS). RESULTS: The analysis confirmed the positive effect of PARPis in patients with platinum sensitive ROC in case of germinal or somatic BRCA mutations. Specifically, HR for PFS was 0.26, 95% CI 0.21-0.31, p < 0.00001 for the mutation of BRCA gene and 0.24, 95%, CI 0.12-0.48, p < 0.0001 for the somatic alteration. In addition, in the HRD population, studies that analysed the efficacy of PARPis reported a PFS improvement with HR 0.34, 95% CI 0.26-0.43, p < 0.00001. Finally, our analysis confirms the role of these drugs in prolonging PFS in the whole population with HR 0.36, 95% CI 0.32-0.42, p < 0.00001, although to a lesser extent, with a significant improvement even in wild type cancers with HR 0.49, 95%, CI 0.41-0.59, p < 0.00001). CONCLUSIONS: PARPis are effective regardless of BRCA mutational status. Future investigations are necessary to explore the use of different PARPis as monotherapy, comparing them among each other in terms of efficacy and toxicity, and exploring their potential re-use.
Authors: T M Zavarikina; S V Khokhlova; A S Tyulyandina; G N Khabas; A V Asaturova; Yu V Nosova; P K Brenner; M A Kapralova; D S Khodirev; M B Stenina Journal: Bull Exp Biol Med Date: 2021-10-28 Impact factor: 0.804