Antitumor efficacy of PARP inhibitors in homologous recombination deficient carcinomas. Issue 5 (23rd February 2019)

• Record Type: Journal Article
• Authors: Yi, Tianjin; Feng, Yi; Sundaram, Ravi; Tie, Yan; Zheng, Heng; Qian, Yanping; You, Di; Yi, Tao; Wang, Ping; Zhao, Xia
• Is Part Of: International journal of cancer. Volume 145:Issue 5(2019)
• Page Start: 1209
• Page End: 1220
• Publication Date: 2019-02-23
• Subjects: PARP inhibitors -- homologous recombination deficient -- BRCA mutations -- clinical outcomes -- meta‐analysis; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.32143
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : PARP inhibitors (PARPis) have remarkable antitumor activity in BRCA mutant ovarian carcinoma. Emerging evidence has shown that responses to PARPis are not limited to BRCA mutant tumors, but could expand to other homologous recombination deficiency (HRD) carcinomas. However, relatively little is known about the efficacy of PARPis in patients with HRD when compared to non‐HRD carriers. In this systematic review, 13 clinical trials were included and analyzed for the treatment effect of PARPis on progression free survival (PFS) and overall survival (OS) for HRD ( BRCA mutant HRD, n = 697; BRCA wild‐type HRD, n = 478) vs . non‐HRD (n = 1, 417) patients. Pooled analyses of the effect of PARPis in both ovarian and nonovarian carcinoma groups showed significantly higher PFS rates at 6 months and 12 months (PFS6 and PFS12) in the HRD subgroup, as compared to the non‐HRD subgroup. Within the HRD subgroup, the BRCA ‐mutant population achieved significantly higher PFS6 (OR: 2.29, 95% CI: 1.03–5.08) and PFS12 (OR: 1.95, 95% CI: 1.26–3.01) when compared to BRCA wild‐type patients. Furthermore, within BRCA wild‐type carcinomas, mutations in other HRD‐related genes also led to increased PFS6 (OR: 1.72, 95% CI: 1.27–2.43) and PFS12 (OR: 1.85, 95% CI: 1.31–2.62), as compared to non‐HRD counterparts. Therefore, patients with HRD carcinomas exhibited pronounced PFS advantages upon treatment with PARPis, as compared to non‐HRD carcinomas. In addition to BRCA mutations, other non‐ BRCA HRD‐related aberrations may serve as novel biomarkers for the prediction of PARPi efficacy. Abstract : What's new? Emerging evidence has shown that responses to PARP inhibitors (PARPis) could expand to homologous recombination deficiency (HRD) carcinomas other than BRCA mutant tumors. However, little is known about the efficacy of PARPis in patients with HRD when compared to non‐HRD carriers. This meta‐analysis demonstrates significantly improved progression‐free survival (PFS) in the HRD population (including BRCA ‐mutant and wild type) as compared to non‐HRD carriers upon treatment with PARPis. Moreover, BRCA ‐wild type HRD carcinomas exhibited significantly increased PFS rates compared with non‐HRD carriers. The findings point to HRD as a novel biomarker to identify BRCA ‐wild type patients who may benefit from PARPis.