帕博西尼在伴有和不伴有内脏转移的晚期乳腺癌患者管理中的临床考虑。
Clinical considerations of the role of palbociclib in the management of advanced breast cancer patients with and without visceral metastases.
机构信息
Toby Robins Breast Cancer Research Centre, Institute of Cancer Research and Royal Marsden Hospital, London, UK.
Department of Medicine, David Geffen School of Medicine, Los Angeles, USA.
出版信息
Ann Oncol. 2018 Mar 1;29(3):669-680. doi: 10.1093/annonc/mdx797.
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.
背景
本报告评估了哌柏西利联合内分泌治疗（ET）在激素受体阳性、人表皮生长因子受体 2 阴性的晚期乳腺癌（ABC）女性中的疗效和安全性，这些女性有或无内脏转移。
患者和方法
在先前 ET 治疗后疾病进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）中，按照 2：1 的比例随机分配接受 ET（氟维司群或来曲唑）联合哌柏西利或安慰剂治疗。无进展生存期（PFS）、安全性和患者报告的生活质量（QoL）根据先前的治疗和内脏受累情况进行评估。
结果
与 ABC 治疗中未接受 ET 治疗的患者（48.6%，PALOMA-2）相比，先前对 ET 耐药的患者（58.3%，PALOMA-3）中内脏转移的发生率更高。在先前对 ET 耐药且有内脏转移的患者中，哌柏西利联合氟维司群的中位 PFS（mPFS）为 9.2 个月，而安慰剂联合氟维司群为 3.4 个月（HR，0.47；95%CI，0.35-0.61），客观缓解率（ORR）分别为 28.0%和 6.7%。在无内脏转移的患者中，mPFS 为 16.6 个月和 7.3 个月，HR 0.53；95%CI 0.36-0.77。在先前接受过 ET 治疗且在晚期疾病治疗中未接受 ET 的有内脏疾病的患者中，哌柏西利联合来曲唑的 mPFS 为 19.3 个月，安慰剂联合来曲唑为 12.9 个月（HR，0.63；95%CI，0.47-0.85）；ORR 分别为 55.1%和 40.0%；在无内脏疾病的患者中，哌柏西利联合来曲唑的 mPFS 无进展，而安慰剂联合来曲唑的 mPFS 为 16.8 个月（HR，0.50；95%CI，0.36-0.70）。在先前对 ET 耐药且有内脏转移的患者中，与安慰剂联合氟维司群相比，哌柏西利联合氟维司群显著延迟了 QoL 的恶化，而在 ABC 内分泌治疗中未接受治疗的患者中，使用哌柏西利联合来曲唑可维持患者报告的 QoL。
结论
哌柏西利联合 ET 延长了有内脏转移的患者的 mPFS，提高了 ORR，并在先前接受 ABC 治疗的患者中延迟了 QoL 的恶化，为适合内分泌治疗的有内脏转移的患者提供了一种标准治疗选择。
临床试验注册
NCT01942135，NCT01740427。
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