Abstract P1-08-32: Homologous recombination deficiency predicts the response to platinum-based neoadjuvant chemotherapy in patients with early-stage triple-negative breast cancer: A meta-analysis

Abstract

Abstract Background: Recent studies have explored the potential role of homologous recombination deficiency (HRD) as a biomarker and shown that the HRD status may be related to the pCR rate. However, does HRD specifically predict the efficacy of platinum chemotherapy, or only predict the benefit of the pCR, irrespective of the treatment regimen? Is there any difference in the efficacy of platinum supplementation between gBRCA1/2 carriers and HRD tumors without gBRCA mutations? Does the addition of platinum to neoadjuvant chemotherapy for patients without HRD bring no curative effects but only increase adverse reactions? We developed this meta-analysis and included all qualified relevant clinical trials to answer these research questions. Materials and methods: Eligible studies were systematically searched from inception to June 1, 2021, in the PubMed, Embase, Medline, Web of Science, and Cochrane databases, and in the abstracts of the European Society for Medical Oncology Congress and the American Society of Clinical Oncology Annual Meeting. The primary outcome was the pathological complete response (pCR, defined as ypT0/is ypN0) after neoadjuvant chemotherapy. Secondary outcomes included clinical response rates and grade 3 or higher adverse events. Classic forest plots were generated using standard techniques to present the meta-analysis results. Results: A total of 1404 patients were included in the present meta-analysis, of which the HRD status was measurable in 1142 (81.3%) patients, and 723 (51.5%) were confirmed to have HRD. Regardless of the HRD status, platinum-based neoadjuvant treatment was statistically associated with better pCR rates than platinum-free neoadjuvant regimens (51.3% vs. 37.6%, OR 1.93, 95% CI 1.13 - 3.30, p = 0.02). The pCR was higher in HRD patients receiving platinum than those without platinum exposure (56.7% vs. 39.4%, OR 1.95, 95% CI 1.17 - 3.23, p = 0.01), while no significant differences were identified between the platinum and control groups in non-HRD patients (36.5% vs. 20.5%, OR 1.82, 95% CI 0.61 - 5.40, p = 0.28). Irrespective of the treatment arm, the odds ratio of achieving the pCR was 3.35 times higher in patients with HRD than in non-HRD patients (51.6% vs. 27.4%, OR 3.35, 95% CI 1.93 - 5.81, p < 0.01). Moreover, among patients on platinum-based regimens, HRD patients had a significant pCR benefit compared to the non-HRD group (58.3% vs. 33.3%, OR 3.40, 95% CI 1.86 - 6.24, p < 0.01). For those without platinum exposure, the results revealed no difference in pCR rates, irrespective of the HRD status (34.3% vs. 20.5%, OR 1.89, 95% CI 0.81 - 4.43, p = 0.14). Among patients with HRD who received platinum-containing therapy, pooled results demonstrated no statistically significant difference between patients with BRCA mutations and those with BRCA wild-type (70.4% vs. 57.8%, OR 1.84, 95% CI 0.84 - 4.02, p = 0.12). With respect to clinical response rates, while more benefit was observed with the use of platinum in HRD and non-HRD patients, the difference was not statistically significant in the forest plot (85.1% vs. 76.1%, OR 1.97, 95% CI 0.91 - 4.27, p = 0.08). Additionally, our results revealed that grade 3 or higher adverse events were more frequently observed in patients on platinum-based regimens. Conclusion: Platinum-based neoadjuvant chemotherapy is associated with significantly higher pCR rates in early-stage triple-negative breast cancer patients with HRD, irrespective of BRCA status. Adding platinum to neoadjuvant treatment in the non-HRD population increases adverse reactions rather than improving the therapeutic effect. Citation Format: Yuanqi Chen, Liulu Zhang, Minyi Cheng, Xiaosheng Zhuang, Ci-Qiu Yang, Fei Ji, Hong-Fei Gao, Mei Yang, Teng Zhu, Jieqing Li, Kun Wang. Homologous recombination deficiency predicts the response to platinum-based neoadjuvant chemotherapy in patients with early-stage triple-negative breast cancer: A meta-analysis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-08-32.