The Era of PARP inhibitors in ovarian cancer: 'Class Action' or not? A systematic review and meta-analysis

التفاصيل البيبلوغرافية
العنوان: The Era of PARP inhibitors in ovarian cancer: 'Class Action' or not? A systematic review and meta-analysis
المؤلفون: Nicoletta Staropoli, Pierfrancesco Tassone, Vito Barbieri, Angela Salvino, Pierosandro Tagliaferri, Domenico Ciliberto, Teresa Del Giudice, Francesco Grillone, Antonio Russo, Maria Cucè, Eleonora Iuliano
المساهمون: Staropoli, Nicoletta, Ciliberto, Domenico, Del Giudice, Teresa, Iuliano, Eleonora, Cucè, Maria, Grillone, Francesco, Salvino, Angela, Barbieri, Vito, Russo, Antonio, Tassone, Pierfrancesco, Tagliaferri, Pierosandro
بيانات النشر: Elsevier Ireland Ltd, 2018.
سنة النشر: 2018
مصطلحات موضوعية: 0301 basic medicine, Oncology, medicine.medical_specialty, Settore MED/06 - Oncologia Medica, Poly (ADP-Ribose) Polymerase-1, Poly(ADP-ribose) Polymerase Inhibitors, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Ovarian cancer, Internal medicine, medicine, Humans, Meta-analysi, Progression-free survival, Adverse effect, Ovarian Neoplasms, business.industry, Hazard ratio, Hematology, Prognosis, Clinical trial, 030104 developmental biology, PARP inhibitor, 030220 oncology & carcinogenesis, Meta-analysis, Relative risk, Cohort, Female, Randomized clinical trial, Maintenance therapy, business
الوصف: Introduction Carboplatin is the milestone of epithelial ovarian cancer (EOC) treatment, thus response to platinum is the major prognostic factor. Among platinum-sensitive patients, 40% carry a germline or somatic BRCA1/2 mutation. In this scenario a new class of drugs, the PARP inhibitors (PARPis), produced a significant improvement in long-term disease control. In order to make an aggregate evaluation of the impact of these agents, we performed a systematic review and meta-analysis. Patients and Methods Clinical trials were selected by searching “Pubmed” database and abstracts from major cancer meetings. We considered the January 2008 - April 2018 time frame. Progression free survival (PFS) was the primary end-point, toxicities were secondary end-points. Hazard ratios (HRs) of PFS, with confidence intervals, and risk ratios of grade 3–4 toxicity rates, were extracted from retrieved studies and included in the current analysis. Meta-analysis was carried out by the fixed and random effect models. We conducted this meta-analysis to also compare indirectly the efficacy of different PARPis in EOC patients. Results Five randomized trials for a total of 1839 patients were selected and included in the final analysis. In particular, we evaluated a BRCA-mutant cohort (871 patients) with a pooled HR 0.25 (95%CI 0.21-0.31) and the BRCA-wild type cohort (836 patients) with a pooled HR 0.41 (95%CI 0.31-0.55), respectively. Regarding safety profile, no significant differences were detected in all grade toxicities, however, taking into account 3–4 grade toxicities and SAEs (severe adverse events), we show that rucaparib-treated patients reported major abdominal pain events, while niraparib-treated patients were associated with the highest percentage of haematological toxicities, hypothesizing a drug effect for the safety analysis. In the indirect comparisons, significant differences were not detected on PFS for the different agents. Conclusions We confirm a significant benefit in survival outcome of PARPis for EOC patients with a “class effect” on the bases of narrow CI and indirect comparisons in the different groups. Therefore, we underline that this strategy is of special value in BRCA-mutated patients because genetic testing allows best patient selection for all PARPis with the added value of individualized prevention in familiars.
اللغة: English
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ce94b6b66d1bf4982c1662dd47dbf8acTest
http://hdl.handle.net/10447/298741Test
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....ce94b6b66d1bf4982c1662dd47dbf8ac
قاعدة البيانات: OpenAIRE