哌柏西利联合氟维司群治疗晚期乳腺癌的总生存期

Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer.

机构信息

From the Institute of Cancer Research and Royal Marsden Hospital, London (N.C.T.); David Geffen School of Medicine at University of California, Los Angeles, Santa Monica (D.J.S.), and Pfizer Oncology, San Diego (X.H.) - both in California; National Cancer Center, Goyang-si, Gyeonggi-do (J.R.), and Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul (S.-A.I.) - both in South Korea; Dnipropetrovsk Medical Academy, City Multiple-Discipline Clinical Hospital 4, Dnipropetrovsk, Ukraine (I.B.); National Hospital Organization Osaka National Hospital, Osaka (N.M.), and Aichi Cancer Center Hospital, Nagoya (H.I.) - both in Japan; Istituto Europeo di Oncologia (M. Colleoni) and Pfizer Oncology (C.G.) - both in Milan; Abramson Cancer Center, University of Pennsylvania, Philadelphia (A.D.), and Pfizer Oncology, Collegeville (C.H.B.) - both in Pennsylvania; Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, VIC, Australia (S. Loi); Tom Baker Cancer Centre, University of Calgary, Calgary, AB, Canada (S.V.); Brustzentrum der Universität München, Munich (N.H.), and the German Breast Group, Neu-Isenburg (S. Loibl) - both in Germany; Institut Gustave Roussy, Villejuif, France (F.A.); Pfizer Oncology, Cambridge, MA (K.P.T.); and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Feinberg School of Medicine, Chicago (M. Cristofanilli).

出版信息

N Engl J Med. 2018 Nov 15;379(20):1926-1936. doi: 10.1056/NEJMoa1810527. Epub 2018 Oct 20.

DOI:10.1056/NEJMoa1810527

PMID:30345905

Abstract

BACKGROUND

The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor palbociclib, in combination with fulvestrant therapy, prolongs progression-free survival among patients with hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. We report the results of a prespecified analysis of overall survival.

METHODS

We randomly assigned patients with hormone-receptor-positive, HER2-negative advanced breast cancer who had progression or relapse during previous endocrine therapy to receive palbociclib plus fulvestrant or placebo plus fulvestrant. We analyzed overall survival; the effect of palbociclib according to the prespecified stratification factors of presence or absence of sensitivity to endocrine therapy, presence or absence of visceral metastatic disease, and menopausal status; the efficacy of subsequent therapies after disease progression; and safety.

RESULTS

Among 521 patients who underwent randomization, the median overall survival was 34.9 months (95% confidence interval [CI], 28.8 to 40.0) in the palbociclib-fulvestrant group and 28.0 months (95% CI, 23.6 to 34.6) in the placebo-fulvestrant group (hazard ratio for death, 0.81; 95% CI, 0.64 to 1.03; P=0.09; absolute difference, 6.9 months). CDK4/6 inhibitor treatment after the completion of the trial regimen occurred in 16% of the patients in the placebo-fulvestrant group. Among 410 patients with sensitivity to previous endocrine therapy, the median overall survival was 39.7 months (95% CI, 34.8 to 45.7) in the palbociclib-fulvestrant group and 29.7 months (95% CI, 23.8 to 37.9) in the placebo-fulvestrant group (hazard ratio, 0.72; 95% CI, 0.55 to 0.94; absolute difference, 10.0 months). The median duration of subsequent therapy was similar in the two groups, and the median time to the receipt of chemotherapy was 17.6 months in the palbociclib-fulvestrant group, as compared with 8.8 months in the placebo-fulvestrant group (hazard ratio, 0.58; 95% CI, 0.47 to 0.73; P<0.001). No new safety signals were observed with 44.8 months of follow-up.

CONCLUSIONS

Among patients with hormone-receptor-positive, HER2-negative advanced breast cancer who had sensitivity to previous endocrine therapy, treatment with palbociclib-fulvestrant resulted in longer overall survival than treatment with placebo-fulvestrant. The differences in overall survival in the entire trial group were not significant. (Funded by Pfizer; PALOMA-3 ClinicalTrials.gov number, NCT01942135 .).

摘要

背景

细胞周期蛋白依赖性激酶 4 和 6（CDK4/6）抑制剂哌柏西利联合氟维司群治疗可延长激素受体阳性、人表皮生长因子受体 2（HER2）阴性晚期乳腺癌患者的无进展生存期。我们报告了预先设定的总生存期分析结果。

方法

我们将先前内分泌治疗期间进展或复发的激素受体阳性、HER2 阴性晚期乳腺癌患者随机分配，接受哌柏西利联合氟维司群或安慰剂联合氟维司群治疗。我们分析了总生存期；根据预先设定的分层因素，即内分泌治疗敏感性、是否存在内脏转移疾病以及绝经状态，评估哌柏西利的疗效；疾病进展后后续治疗的疗效；以及安全性。

结果

在 521 名接受随机分组的患者中，哌柏西利联合氟维司群组的中位总生存期为 34.9 个月（95%置信区间[CI]，28.8 至 40.0），安慰剂联合氟维司群组为 28.0 个月（95%CI，23.6 至 34.6）（死亡风险比，0.81；95%CI，0.64 至 1.03；P=0.09；绝对差异，6.9 个月）。安慰剂联合氟维司群组中，有 16%的患者在完成试验方案后接受了 CDK4/6 抑制剂治疗。在 410 名对先前内分泌治疗敏感的患者中，哌柏西利联合氟维司群组的中位总生存期为 39.7 个月（95%CI，34.8 至 45.7），安慰剂联合氟维司群组为 29.7 个月（95%CI，23.8 至 37.9）（风险比，0.72；95%CI，0.55 至 0.94；绝对差异，10.0 个月）。两组后续治疗的中位持续时间相似，哌柏西利联合氟维司群组中位开始化疗时间为 17.6 个月，安慰剂联合氟维司群组为 8.8 个月（风险比，0.58；95%CI，0.47 至 0.73；P<0.001）。随访 44.8 个月未观察到新的安全性信号。