Clinical considerations of the role of palbociclib in the management of advanced breast cancer patients with and without visceral metastases

Abstract

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.

Figure 1.

Kaplan–Meier plots of progression-free survival in patients in the PALOMA-3 study with visceral metastases (A), nonvisceral metastases (B), and bone-only disease (C), as well as in patients in the PALOMA-2 study with visceral metastases (D), nonvisceral metastases (E), and bone-only disease (F). HR, hazard ratio; NE, not estimable; NR, not reached.

Figure 1.

Kaplan–Meier plots of progression-free survival in patients in the PALOMA-3 study with visceral metastases (A), nonvisceral metastases (B), and bone-only disease (C), as well as in patients in the PALOMA-2 study with visceral metastases (D), nonvisceral metastases (E), and bone-only disease (F). HR, hazard ratio; NE, not estimable; NR, not reached.

Figure 2.

STEPP analysis results of the PFS treatment effect and baseline TFI in subpopulations of patients in the PALOMA-2 study who received adjuvant therapy (A), patients who received adjuvant therapy and had visceral metastases (B), and patients who received adjuvant therapy and had nonvisceral metastases (C). TFI, treatment-free interval (for the purposes of this study, TFI was considered equivalent to disease-free interval [prespecified] in the PALOMA-2 study and was defined as the time from the end of [neo]adjuvant treatment to disease recurrence); PFS, progression-free survival; STEPP, subpopulation treatment effect pattern plot.

Figure 3.

Kaplan–Meier plots of time to deterioration of QoL based on the EORTC QLQ-C30 in patients with visceral metastases (A) and in patients without visceral metastases (B) in the PALOMA-3 study and time to deterioration of FACT-B total score in patients with visceral metastases (C) and without visceral metastases (D) in the PALOMA-2 study. EORTC, European Organisation for Research and Treatment of Cancer; HR, hazard ratio; QoL, health-related quality of life; NE, not estimable; NR, not reached; QLQ-C30, EORTC quality-of-life questionnaire.

Figure 3.

Kaplan–Meier plots of time to deterioration of QoL based on the EORTC QLQ-C30 in patients with visceral metastases (A) and in patients without visceral metastases (B) in the PALOMA-3 study and time to deterioration of FACT-B total score in patients with visceral metastases (C) and without visceral metastases (D) in the PALOMA-2 study. EORTC, European Organisation for Research and Treatment of Cancer; HR, hazard ratio; QoL, health-related quality of life; NE, not estimable; NR, not reached; QLQ-C30, EORTC quality-of-life questionnaire.