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BRCA1 Versus BRCA2 and PARP Inhibitors Efficacy in Solid Tumors:A Meta-Analysis of Randomized Controlled Trials
Shan Li1, Li Tao2, Haiyun Dai3
1Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Background:
BRCA2 mutation has a more substantial impact on the homologous recombination and superior therapeutic response to platinum-based chemotherapy than BRCA1 mutation. Whether BRCA2-mutated patients could benefit more from PARPi than BRCA1-mutated patients remains unclear. We performed a meta-analysis to assess the efficacy difference of PARPi between BRCA1 mutation carriers and BRCA2 mutation carriers.
Methods:
Pubmed, Embase, and Cochrane Library were comprehensively searched for randomized controlled trials (RCTs) of PARPi that had available hazard ratios (HRs) of progression-free survival (PFS) in both BRCA1-mutated population and BRCA2-mutated population. We calculated the pooled PFS HRs and 95%CI using randomized-effect models, and the difference between the two estimates was compared by interaction test.
Results:
A total of 11 eligible RCTs of high quality were identified through search. Overall, 1544 BRCA1 mutation carriers and 1191 BRCA2 mutation carriers were included in the final analysis. The pooled PFS HR was 0.42 (95% CI: 0.35-0.50) in BRCA1-mutated patients who were treated with PARPi compared with patients in the control group. In BRCA2-mutated patients treated with PARPi, the pooled PFS HR compared with the control groups was 0.35 (95% CI: 0.24-0.51). The difference in efficacy of PARPi was not significant between the two subgroups (P heterogeneity = 0.40, for interaction).
Conclusion:
BRCA1-mutated patients and BRCA2-mutated patients could benefit from PARPi, and the efficacy is comparable. Currently, there is no evidence that BRCA2-mutated patients would benefit more from PARPi than BRCA1-mutated patients.
Systematic Review Registration:
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42020214582.
Insights
PARP inhibitors (PARPi) offer comparable benefits for both BRCA1 and BRCA2 mutation carriers. This meta-analysis found no significant difference in efficacy between BRCA1-mutated and BRCA2-mutated patients receiving PARPi therapy.
Area of Science:
- Oncology
- Genetics
- Clinical Trials
Background:
- BRCA2 mutations impact homologous recombination more than BRCA1 mutations, influencing chemotherapy response.
- The comparative efficacy of PARP inhibitors (PARPi) between BRCA1 and BRCA2 mutation carriers is not well-established.
- This meta-analysis investigates the differential efficacy of PARPi in BRCA1- versus BRCA2-mutated patients.
Approach:
- A systematic literature search of PubMed, Embase, and Cochrane Library was conducted for relevant randomized controlled trials (RCTs).
- RCTs with available hazard ratios (HRs) for progression-free survival (PFS) in both BRCA1 and BRCA2 mutated populations were included.
- Pooled PFS HRs and 95% CIs were calculated using random-effect models, with interaction tests to compare subgroup efficacy.
Key Points:
- Eleven high-quality RCTs involving 1544 BRCA1 and 1191 BRCA2 mutation carriers were analyzed.
- PARPi demonstrated significant PFS benefits in both BRCA1-mutated (HR=0.42) and BRCA2-mutated (HR=0.35) patients.
- The efficacy of PARPi was comparable between BRCA1 and BRCA2 mutation carriers (Pinteraction=0.40).
Conclusions:
- Both BRCA1-mutated and BRCA2-mutated patients derive significant benefits from PARPi therapy.
- The efficacy of PARPi is comparable across both BRCA1 and BRCA2 mutation subgroups.
- Current evidence does not support a greater benefit of PARPi for BRCA2-mutated patients compared to BRCA1-mutated patients.
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