Kim Esther S, Scott Lesley J
Springer, Private Bag 65901, Mairangi Bay, 0754, Auckland, New Zealand.
Target Oncol. 2017 Jun;12(3):373-383. doi: 10.1007/s11523-017-0492-7.
Oral palbociclib (Ibrance®) is a first-in-class, highly selective inhibitor of cyclin-dependent kinases 4 and 6 (i.e. a CDK4/6 inhibitor). It is indicated for the treatment of women with HR-positive, HER2-negative advanced or metastatic breast cancer, in combination with an aromatase inhibitor as initial endocrine-based therapy, and in combination with fulvestrant (with or without a luteinizing hormone-releasing hormone agonist) in those previously treated with endocrine therapy. In clinical trials, palbociclib in combination with letrozole as initial endocrine-based therapy in postmenopausal women (PALOMA-1 and PALOMA-2), or in combination with fulvestrant in pre-, peri-, or postmenopausal women with disease progression after endocrine therapy (PALOMA-3), significantly prolonged progression-free survival (PFS) and improved clinical benefit response (CBR) rates. Neutropenia was the most commonly reported any-grade and grade ≥ 3 adverse event. It was infrequently associated with febrile neutropenia (<2%) and generally manageable with a palbociclib dose delay, interruption or reduction, without the routine use of growth factors, and without affecting efficacy. In conclusion, oral palbociclib combination therapy is a valuable emerging option for use in patients with HR-positive, HER2-negative advanced or metastatic breast cancer.
口服哌柏西利（爱博新®）是一种一流的、高选择性细胞周期蛋白依赖性激酶4和6抑制剂（即CDK4/6抑制剂）。它适用于治疗激素受体（HR）阳性、人表皮生长因子受体2（HER2）阴性的晚期或转移性乳腺癌女性患者，与芳香化酶抑制剂联合作为初始内分泌治疗，以及与氟维司群联合（无论有无促黄体生成素释放激素激动剂）用于既往接受过内分泌治疗的患者。在临床试验中，哌柏西利与来曲唑联合作为绝经后女性的初始内分泌治疗（PALOMA-1和PALOMA-2），或与氟维司群联合用于内分泌治疗后疾病进展的绝经前、围绝经期或绝经后女性（PALOMA-3），显著延长了无进展生存期（PFS）并提高了临床获益反应（CBR）率。中性粒细胞减少是最常报告的任何级别和≥3级不良事件。它很少与发热性中性粒细胞减少相关（<2%），通常通过延迟、中断或减少哌柏西利剂量来控制，无需常规使用生长因子，且不影响疗效。总之，口服哌柏西利联合治疗是HR阳性、HER2阴性晚期或转移性乳腺癌患者一种有价值的新兴治疗选择。
