Cruz Giovanna I, Kane Kaitlyn L, Matsuno Rayna K, Sweetnam Connor, Williams Adrienne F O, Toland Liz M, Stone Amy, Berry Anna B, Izano Monika A, Lee Liam C, Earla Jagadeswara R, Brown Thomas D, Drescher Charles W, Kaplan Henry G, Kothari Smita, Sillah Arthur, Jones Gieira
Insights, Syapse Holdings, Inc., West Chester, PA, United States.
Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, United States.
Oncologist. 2025 Aug 4;30(8). doi: 10.1093/oncolo/oyaf100.
Poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPis) are indicated for treatment of tumors with breast cancer susceptibility genes BRCA1/2 mutations and homologous recombination deficiency (HRD). Little is known about differences in care by BRCA1/2 and HRD status for breast and ovarian cancers.
We investigated clinical characteristics, treatment, clinical outcomes, and health-care resource utilization by BRCA1/2 or HRD status among patients diagnosed between 2018-2020 with HER2-negative metastatic breast (mBC) and advanced epithelial ovarian cancer (aEOC) in the United States community healthcare setting.
The study included 314 patients with mBC and 465 with aEOC. Patients with mBC carrying a BRCA1/2 mutation were younger and had a higher proportion of triple negative cancer than non-carriers (50% vs 38%). Only 8% of eligible patients received a PARPi in first-line (1L) and 18% in second-line (2L) of treatment for mBC. In aEOC, patients with HRD were younger and a higher proportion received 1L maintenance treatment with a PARPi than patients with non-HRD tumors (95% vs 66%). In aEOC, patients without HRD had greater healthcare resource use. Patients with BRCA-mutated tumors had poorer overall survival (OS); there were no differences in OS by HRD status in aEOC.
This study demonstrated differences in treatment by BRCA1/2 and HRD status. There was low PARPi uptake among patients with BRCA-mutated mBC but not among patients with aEOC. In aEOC, the cost to "treat all" may outweigh benefits; identifying patients without HRD likely to benefit from PARPis is needed.
聚(腺苷二磷酸[ADP] - 核糖)聚合酶抑制剂(PARPis)被用于治疗具有乳腺癌易感基因BRCA1/2突变和同源重组缺陷(HRD)的肿瘤。关于乳腺癌和卵巢癌患者基于BRCA1/2及HRD状态的治疗差异,人们了解甚少。
我们调查了2018年至2020年间在美国社区医疗环境中被诊断为HER2阴性转移性乳腺癌(mBC)和晚期上皮性卵巢癌(aEOC)的患者,根据BRCA1/2或HRD状态的临床特征、治疗情况、临床结局以及医疗资源利用情况。
该研究纳入了314例mBC患者和465例aEOC患者。携带BRCA1/2突变的mBC患者比未携带者更年轻,三阴性癌比例更高(50%对38%)。在mBC治疗的一线(1L)中,只有8%的符合条件患者接受了PARPi治疗,二线(2L)治疗中这一比例为18%。在aEOC中,HRD患者更年轻,与非HRD肿瘤患者相比,接受PARPi一线维持治疗的比例更高(95%对66%)。在aEOC中,非HRD患者的医疗资源使用更多。BRCA突变肿瘤患者的总生存期(OS)较差;在aEOC中,OS在HRD状态方面无差异。
本研究表明了基于BRCA1/2及HRD状态的治疗差异。BRCA突变的mBC患者中PARPi的使用率较低,但aEOC患者并非如此。在aEOC中,“全面治疗”的成本可能超过收益;需要识别出可能从PARPis中获益的非HRD患者。