Schickli M Alexandra, Berger Michael J, Lustberg Maryam, Palettas Marilly, Vargo Craig A
1 The Stefanie Spielman Comprehensive Breast Center, Columbus, OH, USA.
2 Center for Biostatistics and Bioinformatics at The Ohio State University, Columbus, OH, USA.
J Oncol Pharm Pract. 2019 Sep;25(6):1374-1380. doi: 10.1177/1078155218794847. Epub 2018 Aug 22.
The management of endocrine therapy resistance is one of the most challenging facets of advanced breast cancer treatment. Palbociclib is an inhibitor of cyclin-dependent kinases 4 and 6 approved for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer in combination with fulvestrant in postmenopausal women with disease progression following endocrine therapy. However, treatment responsiveness of tumors to palbociclib after multiple lines of endocrine therapy is not clearly established. The purpose of this study was to determine the efficacy of palbociclib and letrozole in patients pretreated with one or more lines of endocrine therapy.
This was a single-center, retrospective cohort study of all postmenopausal hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer patients who received palbociclib and letrozole as a second-line endocrine therapy or beyond (and no prior cyclin-dependent kinases 4 and 6 inhibitor therapy) between February 1, 2015, and July 31, 2016. The primary objective was to evaluate time to treatment failure of palbociclib in combination with letrozole as a second-line of therapy or beyond.
Fifty-three patients meeting eligibility criteria were included in the analysis. For the primary outcome, the median time to treatment failure of palbociclib and letrozole was 6.3 months (95% CI 3.1-7.4 months). Progression-free survival of palbociclib and letrozole therapy was 6.4 months (95% CI 4.9-8.3 months).
Palbociclib and letrozole therapy is a viable, effective treatment option for metastatic breast cancer patients who were not exposed to cyclin-dependent kinases 4 and 6 inhibitors as a first-line endocrine therapy. The benefits of palbociclib and letrozole therapy were seen without excessive toxicity, and although neutropenia was common, it may be managed with dose reduction.
内分泌治疗耐药的管理是晚期乳腺癌治疗中最具挑战性的方面之一。哌柏西利是细胞周期蛋白依赖性激酶4和6的抑制剂，被批准用于治疗激素受体阳性、人表皮生长因子受体2阴性的晚期或转移性乳腺癌，与氟维司群联合用于内分泌治疗后疾病进展的绝经后女性。然而，经过多线内分泌治疗后肿瘤对哌柏西利的治疗反应性尚未明确确立。本研究的目的是确定哌柏西利和来曲唑在接受过一线或多线内分泌治疗的患者中的疗效。
这是一项单中心回顾性队列研究，研究对象为2015年2月1日至2016年7月31日期间接受哌柏西利和来曲唑作为二线或更后线内分泌治疗（且之前未接受过细胞周期蛋白依赖性激酶4和6抑制剂治疗）的所有绝经后激素受体阳性、人表皮生长因子受体2阴性的转移性乳腺癌患者。主要目的是评估哌柏西利联合来曲唑作为二线或更后线治疗的治疗失败时间。
53例符合纳入标准的患者纳入分析。对于主要结局，哌柏西利和来曲唑的中位治疗失败时间为6.3个月（95%CI 3.1 - 7.4个月）。哌柏西利和来曲唑治疗的无进展生存期为6.4个月（95%CI 4.9 - 8.3个月）。
对于未接受过细胞周期蛋白依赖性激酶4和6抑制剂作为一线内分泌治疗的转移性乳腺癌患者，哌柏西利和来曲唑治疗是一种可行、有效的治疗选择。哌柏西利和来曲唑治疗有疗效且无过度毒性，虽然中性粒细胞减少很常见，但可通过剂量减少进行处理。
