Background This report assesses the efficacy and safety of palbociclib plus endocrine therapy (ET) in women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC) with or without visceral metastases. Patients and methods Pre- and postmenopausal women with disease progression following prior ET (PALOMA-3; N = 521) and postmenopausal women untreated for ABC (PALOMA-2; N = 666) were randomized 2 : 1 to ET (fulvestrant or letrozole, respectively) plus palbociclib or placebo. Progression-free survival (PFS), safety, and patient-reported quality of life (QoL) were evaluated by prior treatment and visceral involvement. Results Visceral metastases incidence was higher in patients with prior resistance to ET (58.3%, PALOMA-3) than in patients naive to ET in the ABC setting (48.6%, PALOMA-2). In patients with prior resistance to ET and visceral metastases, median PFS (mPFS) was 9.2 months with palbociclib plus fulvestrant versus 3.4 months with placebo plus fulvestrant [hazard ratio (HR), 0.47; 95% confidence interval (CI), 0.35-0.61], and objective response rate (ORR) was 28.0% versus 6.7%, respectively. In patients with nonvisceral metastases, mPFS was 16.6 versus 7.3 months, HR 0.53; 95% CI 0.36-0.77. In patients with visceral disease and naive to ET in the advanced disease setting, mPFS was 19.3 months with palbociclib plus letrozole versus 12.9 months with placebo plus letrozole (HR 0.63; 95% CI 0.47-0.85); ORR was 55.1% versus 40.0%; in patients with nonvisceral disease, mPFS was not reached with palbociclib plus letrozole versus 16.8 months with placebo plus letrozole (HR 0.50; 95% CI 0.36-0.70). In patients with prior resistance to ET with visceral metastases, palbociclib plus fulvestrant significantly delayed deterioration of QoL versus placebo plus fulvestrant, whereas patient-reported QoL was maintained with palbociclib plus letrozole in patients naive to endocrine-based therapy for ABC. Conclusions Palbociclib plus ET prolonged mPFS in patients with visceral metastases, increased ORRs, and in patients previously treated for ABC, delayed QoL deterioration, presenting a standard treatment option among patients with visceral metastases amenable to endocrine-based therapy. Clinical trial registration NCT01942135, NCT01740427.

中文翻译：

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palbociclib在有或无内脏转移的晚期乳腺癌患者管理中的作用的临床考虑。

背景本报告评估帕波西lib +内分泌疗法（ET）在激素受体阳性，人表皮生长因子受体2阴性，患有或不患有内脏转移的女性中的疗效和安全性。患者和方法将先前ET后疾病发展的绝经前和绝经后妇女（PALOMA-3; N = 521）和未接受ABC治疗的绝经后妇女（PALOMA-2; N = 666）随机分配至ET 2：1（氟维司群或来曲唑，分别）加上palbociclib或安慰剂。无进展生存期（PFS），安全性和患者报告的生活质量（QoL）通过事先治疗和内脏受累进行评估。结果先前对ET有抗药性的内脏转移发生率（58.3％，PALOMA-3）高于在ABC环境中未接受ET的患者（48.6％，PALOMA-2）。在先前对ET和内脏转移有耐药性的患者中，palbociclib加氟维司群的中位PFS（mPFS）为9.2个月，而安慰剂加氟维司坦的中位PFS为3.4个月[危险比（HR），0.47；95％的置信区间（CI）为0.35-0.61]，客观响应率（ORR）分别为28.0％和6.7％。在非内脏转移患者中，mPFS为16.6，而7.3个月为HR 0.53。95％CI 0.36-0.77。对于患有内脏疾病且在疾病晚期接受过ET治疗的患者，palbociclib加来曲唑的mPFS为19.3个月，而安慰剂加来曲唑的mPFS为12.9个月（HR 0.63； 95％CI 0.47-0.85）；ORR分别为55.1％和40.0％；在非内脏疾病患者中，palbociclib加来曲唑未达到mPFS，而安慰剂加来曲唑则为16.8个月（HR 0.50； 95％CI 0.36-0.70）。在先天性内脏转移对ET有抗药性的患者中，与安慰剂加氟维司群相比，palbociclib加氟维司群显着延迟了QoL的恶化，而对于单纯接受内分泌治疗的ABC患者，palbociclib加来曲唑维持了患者报告的QoL。结论Palbociclib加ET可延长内脏转移患者的mPFS，ORR升高，以及先前接受过ABC治疗的患者，QoL延迟延迟，这是适合内分泌治疗的内脏转移患者的标准治疗选择。临床试验注册NCT01942135，NCT01740427。而未接受基于内分泌的ABC治疗的患者，使用palbociclib加来曲唑维持患者报告的QoL。结论Palbociclib加ET可延长内脏转移患者的mPFS，ORR升高，以及先前接受过ABC治疗的患者，QoL延迟延迟，这是适合内分泌治疗的内脏转移患者的标准治疗选择。临床试验注册NCT01942135，NCT01740427。而未接受基于内分泌的ABC治疗的患者，使用palbociclib加来曲唑维持患者报告的QoL。结论Palbociclib加ET可延长内脏转移患者的mPFS，ORR升高，以及先前接受过ABC治疗的患者，QoL延迟延迟，这是适合内分泌治疗的内脏转移患者的标准治疗选择。临床试验注册NCT01942135，NCT01740427。