Susan F. Smith Center for Women's Cancers, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston.
Division of Hematology and Oncology, University of Pennsylvania Abramson Cancer Center, Philadelphia.
Ann Oncol. 2019 Sep 1;30(9):1514-1520. doi: 10.1093/annonc/mdz198.
The CDK4/6 inhibitor palbociclib prolongs progression-free survival in hormone receptor-positive/HER2-negative (HR+/HER2-) metastatic breast cancer when combined with endocrine therapy. This phase II trial was designed to determine the feasibility of adjuvant palbociclib and endocrine therapy for early breast cancer.
Eligible patients with HR+/HER2- stage II-III breast cancer received 2 years of palbociclib at 125 mg daily, 3 weeks on/1 week off, with endocrine therapy. The primary end point was discontinuation from palbociclib due to toxicity, non-adherence, or events related to tolerability. A discontinuation rate of 48% or higher would indicate the treatment duration of 2 years was not feasible, and was evaluated under a binomial test using a one-sided α = 0.025.
Overall, 162 patients initiated palbociclib; over half had stage III disease (52%) and most received prior chemotherapy (80%). A total of 102 patients (63%) completed 2 years of palbociclib; 50 patients discontinued early for protocol-related reasons (31%, 95% CI 24% to 39%, P = 0.001), and 10 discontinued due to protocol-unrelated reasons. The cumulative incidence of protocol-related discontinuation was 21% (95% CI 14% to 27%) at 12 months from start of treatment. Rates of palbociclib-related toxicity were congruent with the metastatic experience, and there were no cases of febrile neutropenia. Ninety-one patients (56%) required at least one dose reduction.
Adjuvant palbociclib is feasible in early breast cancer, with a high proportion of patients able to complete 2 years of therapy. The safety profile in the adjuvant setting mirrors that observed in metastatic disease, with approximately half of the patients requiring dose-modification. As extended duration adjuvant palbociclib appears feasible and tolerable for most patients, randomized phase III trials are evaluating clinical benefit in this population.
CLINICALTRIALS.GOV REGISTRATION: NCT02040857.
CDK4/6 抑制剂哌柏西利与内分泌治疗联合使用可延长激素受体阳性/HER2 阴性（HR+/HER2-）转移性乳腺癌患者的无进展生存期。本 II 期试验旨在确定辅助性哌柏西利联合内分泌治疗早期乳腺癌的可行性。
符合条件的 HR+/HER2-Ⅱ-Ⅲ期乳腺癌患者接受为期 2 年的哌柏西利 125mg 每日一次，每 3 周用药 1 周停药，同时接受内分泌治疗。主要终点是因毒性、不依从或与耐受性相关的事件而停止使用哌柏西利。如果停药率达到 48%或更高，则表明 2 年的治疗时间不可行，采用单侧 α=0.025 的二项式检验进行评估。
总体而言，162 例患者开始使用哌柏西利；超过一半的患者为 III 期疾病（52%），大多数患者接受过化疗（80%）。共有 102 例（63%）患者完成了 2 年的哌柏西利治疗；50 例患者因方案相关原因提前停药（31%，95%CI 24%至 39%，P=0.001），10 例患者因方案不相关原因停药。治疗开始后 12 个月时，因方案相关原因停药的累积发生率为 21%（95%CI 14%至 27%）。哌柏西利相关毒性发生率与转移性疾病一致，无发热性中性粒细胞减少症病例。91 例（56%）患者至少需要减少 1 剂药物剂量。
辅助性哌柏西利在早期乳腺癌中是可行的，有很高比例的患者能够完成 2 年的治疗。辅助治疗中的安全性与转移性疾病中观察到的安全性一致，大约一半的患者需要剂量调整。由于延长辅助性哌柏西利的治疗时间对大多数患者似乎是可行且可耐受的，因此正在进行随机 III 期临床试验评估该人群的临床获益。
临床试验.gov 注册号：NCT02040857。
