Clinical Considerations of the Role of Palbociclib in the Management of Advanced Breast Cancer Patients With and Without Visceral Metastases
Mené sur 1 187 patientes atteintes d'un cancer du sein ER+ HER2+ de stade avancé avec ou sans métastases viscérales, cet essai randomisé évalue l'efficacité, du point de vue de la survie sans progression et de la qualité de vie, et la toxicité de l'ajout du palbociclib à une hormonothérapie (fulvestrant ou létrozole)
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 endocrine therapy 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 naive to endocrine therapy 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 registrationNCT01942135, NCT01740427
Annals of Oncology 2018