Department of Medicine (Hematology/Oncology), University of California San Francisco, Comprehensive Cancer Center, San Francisco, CA.
Division of Hematology/Oncology, David Geffen School of Medicine at UCLA, Santa Monica, CA.
Clin Breast Cancer. 2020 Apr;20(2):e173-e180. doi: 10.1016/j.clbc.2019.08.009. Epub 2019 Sep 5.
In PALOMA-2, palbociclib + letrozole significantly prolonged progression-free survival (PFS) versus placebo + letrozole in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER/HER2) advanced breast cancer (ABC). We investigated clinical outcomes of patients who achieved or did not achieve a confirmed objective response (OR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (data cutoff: May 31, 2017).
Postmenopausal patients untreated for ER/HER2 ABC were randomized 2:1 to palbociclib + letrozole or placebo + letrozole. Median PFS, median duration of OR, baseline characteristics, and palbociclib exposure were compared in patients with or without OR by treatment arm.
In the intent-to-treat population, OR was achieved by 194 (44%) of 444 and 77 (35%) of 222 patients in the palbociclib and placebo arms, respectively (odds ratio, 1.5; 95% confidence interval [CI], 1.0-2.1; P = .0156). Regardless of treatment, more OR than non-OR patients had de novo metastatic disease (47%-50% and 28%-31%, respectively) and no prior endocrine therapy (55% and 35%-37%, respectively). Rates of palbociclib dose reduction owing to adverse events were similar regardless of OR (41% and 38%, respectively). Among the patients with OR during the study, approximately 50% achieved OR within the first 3 months regardless of treatment. The median PFS was significantly prolonged with palbociclib + letrozole versus placebo + letrozole in patients with measurable disease in both OR (37.2 months; 95% CI, 28.1 months to not estimable vs. 27.4 months; 95% CI, 22.2-31.1 months; hazard ratio, 0.66; 95% CI, 0.47-0.94; P = .009) and non-OR groups (10.9 months; 95% CI, 8.2-11.2 months vs. 5.6 months; 95% CI, 5.3-8.3 months; hazard ratio, 0.72; 95% CI, 0.54-0.97; P = .016).
Palbociclib + letrozole provided significant clinical benefit versus placebo + letrozole to patients with ER/HER2 ABC regardless of achieving RECIST-defined OR. Pfizer; ClinicalTrials.gov: NCT01740427.
在 PALOMA-2 研究中，与安慰剂联合来曲唑相比，哌柏西利联合来曲唑显著延长了雌激素受体阳性/人表皮生长因子受体 2 阴性（ER/HER2）晚期乳腺癌（ABC）患者的无进展生存期（PFS）。我们根据实体瘤反应评价标准（RECIST）1.1 版（数据截止日期：2017 年 5 月 31 日），调查了达到或未达到确认客观缓解（OR）的患者的临床结局。
未接受过 ER/HER2 ABC 治疗的绝经后患者按 2:1 的比例随机分配至哌柏西利联合来曲唑或安慰剂联合来曲唑治疗组。比较了按治疗臂在有或无 OR 患者中的中位 PFS、中位 OR 持续时间、基线特征和哌柏西利暴露情况。
在意向治疗人群中，哌柏西利组和安慰剂组分别有 194（44%）例和 77（35%）例患者达到 OR（比值比，1.5；95%置信区间[CI]，1.0-2.1；P =.0156）。无论治疗情况如何，OR 患者较无 OR 患者更易发生新发转移性疾病（47%-50%和 28%-31%），且无内分泌治疗史（55%和 35%-37%）。因不良事件而减少哌柏西利剂量的发生率在有或无 OR 患者中相似（分别为 41%和 38%）。在研究期间有 OR 的患者中，无论治疗情况如何，约有 50%的患者在 3 个月内达到 OR。与安慰剂联合来曲唑相比，哌柏西利联合来曲唑在可测量疾病患者中均显著延长了 PFS：在 OR 患者中为 37.2 个月（95%CI，28.1 个月至无法评估）和非 OR 患者中为 27.4 个月（95%CI，22.2-31.1 个月）（风险比，0.66；95%CI，0.47-0.94；P =.009）。
与安慰剂联合来曲唑相比，哌柏西利联合来曲唑为 ER/HER2 ABC 患者提供了显著的临床获益，无论患者是否达到 RECIST 定义的 OR。 Pfizer；临床试验.gov：NCT01740427。
