Shao Changxia, Chang Michael S, Lam Fred C, Marley Andrew R, Tang Huilin, Song Yiqing, Miller Chelsey, Brown Madeline, Wan Isabella, Han Jiali, Adeboyeje Gboyega
Merck & Co., Inc, Kenilworth, NJ, USA.
Harvard Medical School, Boston, MA, USA.
J Oncol. 2022 Jul 20;2022:5830475. doi: 10.1155/2022/5830475. eCollection 2022.
Patients with mutations (m), loss-of-function mutations in other homologous recombination repair (HRRm) genes, or tumors that are homologous recombination deficiency positivity (HRD+) demonstrate a robust response to PARPi therapy. We conducted a systematic literature review and meta-analysis to evaluate the prognostic value of m, HRRm, and HRD+ on overall survival (OS) among those treated by chemotherapy or targeted therapy other than PARPi across tumor types. A total of 135 eligible studies were included. Breast cancer (BC) patients with m had a similar overall survival (OS) to those with wild-type (wt) across 18 studies. Ovarian cancer (OC) patients with m had a significantly longer OS than those with wt across 24 studies reporting m and m, with an HR of 0.7 (0.6-0.8). Less OS data were reported for other tumors: 6 studies for m compared with wt in prostate cancer with an HR of 1.9 (1.1-3.2) and 2 studies for m compared with wt in pancreatic cancer with an HR of 1.5 (0.8-3.1). Only 4 studies reported HRD+ by either m or genomic instability score (GIS) ≥ 42 and OS by HRD status. The HR was 0.67 (0.43-1.02) for OS with HRD+ vs. HRD-. A total of 15 studies reported the association between HRRm and OS of cancers in which one or more HRR genes were examined. The HR was 1.0 (0.7-1.4) comparing patients with HRRm to those with HRR wild-type across tumors. Our findings are useful in improving the precision and efficacy of treatment selection in clinical oncology.
携带突变（m）、其他同源重组修复（HRRm）基因功能缺失突变或同源重组缺陷阳性（HRD+）的肿瘤患者对PARPi治疗表现出强烈反应。我们进行了一项系统的文献综述和荟萃分析，以评估m、HRRm和HRD+在接受除PARPi之外的化疗或靶向治疗的不同肿瘤类型患者中对总生存期（OS）的预后价值。共纳入135项符合条件的研究。在18项研究中，携带m的乳腺癌（BC）患者与野生型（wt）患者的总生存期（OS）相似。在24项报告m和wt的研究中，携带m的卵巢癌（OC）患者的OS显著长于wt患者，风险比（HR）为0.7（0.6 - 0.8）。其他肿瘤报告的OS数据较少：前列腺癌中6项研究比较了m与wt，HR为1.9（1.1 - 3.2）；胰腺癌中2项研究比较了m与wt，HR为1.5（0.8 - 3.1）。只有4项研究通过m或基因组不稳定评分（GIS）≥42报告HRD+，并按HRD状态报告OS。HRD+与HRD-相比，OS的HR为0.67（0.43 - 1.02）。共有15项研究报告了HRRm与癌症OS之间的关联，其中检测了一个或多个HRR基因。跨肿瘤类型比较，HRRm患者与HRR野生型患者的HR为1.0（0.7 - 1.4）。我们的研究结果有助于提高临床肿瘤学中治疗选择的精准性和疗效。
