Efficacy and safety of PARP inhibitors in patients with BRCA-mutated advanced breast cancer: A meta-analysis and systematic review

Abstract

Objective This meta-analysis aimed to investigate the efficacy and safety of poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors in BRCA- mutated advanced breast cancer patients comprehensively. Methods We conducted a systematic literature research through PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, China National Knowledge Infrastructure (CNKI), wanfang, China Biology Medicine disc (CBMdisc), and ClinicalTrials.gov from inception to January 2021. Randomized controlled trials (RCTs) with available data comparing PARP inhibitors versus control therapy in BRCA -mutated advanced breast cancer were eligible for analysis. Statistical analyses were performed with Review Manager (RevMan) version 5.4 and R version 4.0.3. Results 1706 studies were retrieved in total, and 4 RCTs with 1540 patients were eligible for meta-analysis finally. The results showed that progression-free survival (PFS) and overall survival (OS) were significantly improved in germline BRCA -mutated breast cancer patients with PARP inhibitors (HR 0.64, 95% CI [0.56–0.74]; HR 0.86, 95% CI [0.74–0.99], respectively) with no significant heterogeneity across studies (I 2 = 22%, χ 2 p = 0.28; I 2 = 0%, χ 2 p = 0.70, respectively). There was no significant difference in the overall adverse events (AEs), grade≥3 AEs and AEs leading to treatment discontinuation between PARP inhibitor arms and control arms (RR 1.01, 95% CI [0.99–1.02]; RR 0.95, 95% CI [0.83–1.09]; RR 1.17, 95% CI [0.87–1.57], respectively). Based on the available data, PARP inhibitors provided comparable or better results than control arms in improving the quality of life in BRCA -mutated advanced breast cancer patients. Conclusions PARP inhibitors prolonged PFS and OS among patients with BRCA -mutated advanced breast cancer with tolerable safety and improved quality of life.

Efficacy and safety of PARP inhibitors in the treatment of BRCA-mutated breast cancer: An updated systematic review and meta-analysis of randomized controlled trials

“…In addition, our meta-analysis also evaluated the e cacy of PARPis in combination with chemotherapeutic agents. Although OS and ORR did not improve, PFS had signi cant bene ts (HR 0.71 [95%CI, 0.59 to 0.85], p = 0.00002), which is consistent with the strati ed results of our PARPis combination therapy (43). Meanwhile, our analysis also noted that there was no signi cant difference in bene t between monotherapy and combination therapy, which may provide strong evidence for future clinical drug combination.…”

PARP Inhibition and Beyond in BRCA-Associated Breast Cancer in Women: A State-Of-The-Art Summary of Preclinical Research on Risk Reduction and Clinical Benefits

“…A subanalysis of their data confirmed these positive results for both BRCA1-mutant carriers (HR 0.65; 95% CI: 0.53–0.78) and BRCA2-mutant carriers (HR 0.63; 95% CI: 0.51–0.76) as well as for triple-negative cases (HR 0.62; 95% CI: 0.50–0.77). Further to this, Sun et al [ 39 ] showed that progression-free survival significantly improved using the single-agent PARP inhibitor in BRCA1 patients (HR 0.64; 95% CI: 0.53–0.79) with similar results in triple-negative breast cancer patients (HR 0.65; 95% CI: 0.54–0.79). These researchers also reported adverse hematological events: neutropenia in 35% of the patients studied, anemia in 29%, and thrombocytopenia in 24%.…”

From Immunohistochemistry to New Digital Ecosystems: A State-of-the-Art Biomarker Review for Precision Breast Cancer Medicine

“…In a recent meta-analysis [ 74 ], PARP inhibitors were found to prolong progression-free and overall survival in patients with BRCA mutations and advanced breast cancers, with tolerable safety and overall improved quality of life. In breast cancers, two PARP inhibitors, olaparib and talazoparib, were recently approved in germline BRCA mutation (gBRCAm ) carriers for the treatment of metastatic HER2-negative breast cancer based on both the OlympiAD [ 75 ] and EMBRACA [ 76 ] trials, respectively.…”