Collins Jenna M, Nordstrom Beth L, McLaurin Kimmie K, Dalvi Tapashi B, McCutcheon Susan C, Bennett James C, Murphy Brian R, Singhal Puneet K, McCrea Charles, Shinde Reshma, Briceno Josefa M
Evidera, 500 Totten Pond Road, 5th Floor, Waltham, MA, 02451, USA.
AstraZeneca Pharmaceuticals, LP, One MedImmune Way, Gaithersburg, MD, 20878, USA.
Oncol Ther. 2021 Dec;9(2):575-589. doi: 10.1007/s40487-021-00162-4. Epub 2021 Jul 25.
Limited data exist on real-world treatment patterns and the effectiveness of cyclin-dependent kinase (CDK) 4/6 inhibitors in germline BRCA (gBRCA)-mutated breast cancer.
Adults with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) treated with CDK4/6 inhibitor therapy between 2013 and 2018 were retrospectively selected from the Flatiron Health database. Patients with known gBRCA status were classified as mutated (gBRCAm) or wild type (gBRCAwt). Time-to-first subsequent therapy or death (TFST) and overall survival (OS) were calculated from the earliest line of therapy with a CDK4/6 inhibitor.
Of 2968 patients with HR+/HER2- mBC receiving a CDK4/6 inhibitor, 859 (28.9%) had known gBRCA status, of whom 9.9% were gBRCAm and 90.1% gBRCAwt. Median (95% confidence interval [CI]) TFST was 10 (7-11) months in the gBRCAm group, 10 (9-11) months in the gBRCAwt group, and 11 (10-12) months in the combined gBRCAwt and unknown gBRCA group; median (95% CI) OS was 26 (21-not estimated), 37 (31-51), and 33 (31-35) months, respectively. Cox models indicated the gBRCAm group had shorter TFST (stratified hazard ratio [sHR] 1.24; 95% CI 0.96-1.59) and OS (sHR 1.50; 95% CI 1.06-2.14) than the gBRCAwt group. The gBRCAm group had shorter TFST (sHR 1.38; 95% CI 1.08-1.75) and OS (sHR 1.22; 95% CI 0.88-1.71) than the combined group.
The results of this real-world study suggest that treatment outcomes with CDK4/6 inhibitors may be worse in patients with gBRCAm mBC than in their counterparts with gBRCAwt and unknown gBRCA status, suggesting potential differences in tumor biology. This result highlights the unmet need in patients with gBRCAm requiring optimized treatment selection and sequencing. Future exploration in larger samples of patients who have had biomarker testing is warranted.
关于细胞周期蛋白依赖性激酶（CDK）4/6抑制剂在种系BRCA（gBRCA）突变型乳腺癌中的实际治疗模式和有效性的数据有限。
从Flatiron Health数据库中回顾性选取2013年至2018年间接受CDK4/6抑制剂治疗的激素受体阳性（HR+）、人表皮生长因子受体2阴性（HER2-）转移性乳腺癌（mBC）成人患者。已知gBRCA状态的患者分为突变型（gBRCAm）或野生型（gBRCAwt）。从最早使用CDK4/6抑制剂治疗开始计算首次后续治疗或死亡时间（TFST）和总生存期（OS）。
在2968例接受CDK4/6抑制剂治疗的HR+/HER2- mBC患者中，859例（28.9%）已知gBRCA状态，其中9.9%为gBRCAm，90.1%为gBRCAwt。gBRCAm组的中位（95%置信区间[CI]）TFST为10（7-11）个月，gBRCAwt组为10（9-11）个月，gBRCAwt和gBRCA状态未知的联合组为11（10-12）个月；中位（95%CI）OS分别为26（21-未估计）、37（31-51）和33（31-35）个月。Cox模型表明，gBRCAm组的TFST（分层风险比[sHR] 1.24；95%CI 0.96-1.59）和OS（sHR 1.50；95%CI 1.06-2.14）比gBRCAwt组短。gBRCAm组的TFST（sHR 1.38；95%CI 1.08-1.75）和OS（sHR 1.22；95%CI 0.88-1.71）比联合组短。
这项真实世界研究的结果表明，gBRCAm mBC患者使用CDK4/6抑制剂的治疗结果可能比gBRCAwt和gBRCA状态未知的患者更差，提示肿瘤生物学可能存在差异。这一结果凸显了gBRCAm患者在优化治疗选择和排序方面未得到满足的需求。有必要对更大样本的进行过生物标志物检测的患者进行进一步探索。
