A Real-World Evidence Study of CDK4/6 Inhibitor Treatment Patterns and Outcomes in Metastatic Breast Cancer by Germline BRCA Mutation Status

被引:39
作者
Collins, Jenna M. [1 ]
Nordstrom, Beth L. [1 ]
McLaurin, Kimmie K. [2 ]
Dalvi, Tapashi B. [2 ]
McCutcheon, Susan C. [3 ]
Bennett, James C. [3 ]
Murphy, Brian R. [1 ]
Singhal, Puneet K. [4 ]
McCrea, Charles [3 ]
Shinde, Reshma [4 ]
Briceno, Josefa M. [2 ]
机构
[1] Evidera, 500 Totten Pond Rd,5th Floor, Waltham, MA 02451 USA
[2] AstraZeneca Pharmaceut LP, One MedImmune Way, Gaithersburg, MD 20878 USA
[3] AstraZeneca, Acad House,136 Hills Rd, Cambridge CB2 8PA, England
[4] Merck & Co Inc, 2000 Galloping Hill Rd, Kenilworth, NJ 07033 USA
关键词
CDK4/6; inhibitors; gBRCA mutation status; Metastatic breast cancer; Survival; Treatment patterns; DX RECURRENCE SCORE; DNA-DAMAGE RESPONSE; CARRIERS; RECEPTORS; ESTROGEN;
D O I
10.1007/s40487-021-00162-4
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Introduction 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. Methods 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. Results 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. Conclusion 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.
引用
收藏
页码:575 / 589
页数:15
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