Palbociclib Plus Letrozole as First-Line Therapy in Postmenopausal Asian Women With Metastatic Breast Cancer: Results From the Phase III, Randomized PALOMA-2 Study

Abstract

Purpose: In PALOMA-2, palbociclib plus letrozole significantly improved progression-free survival (PFS) as initial treatment of estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer. We assessed the benefit of palbociclib plus letrozole in Asians.

Patients and methods: Of 666 enrolled postmenopausal women with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer (no prior treatment of advanced disease), 95 were Asian. Patients were randomly assigned 2:1 to receive palbociclib plus letrozole or placebo plus letrozole. The primary end point was investigator-assessed PFS. Secondary end points were overall survival, objective response, patient-reported outcomes, pharmacokinetics, and safety.

Results: Median PFS was significantly longer in Asian patients who received palbociclib plus letrozole versus placebo plus letrozole (25.7 months [95% CI, 19.2 months to not estimable] v 13.9 months [95% CI, 7.4 to 22.0 months]; hazard ratio, 0.49; 95% CI, 0.27 to 0.87; P = .007). The most common toxicities with palbociclib were hematologic and more frequent among Asians versus non-Asians: neutropenia (any grade, 95.4% v 76.8%; grade 3/4, 89.2% v 62.5%), leukopenia (43.1% v 38.3%; 32.3% v 23.5%), and thrombocytopenia (27.7% v 13.5%; 4.6% v 1.1%). No Asians had febrile neutropenia. Discontinuation rates as a result of adverse events were similar among Asian and non-Asian patients who received palbociclib plus letrozole (10.8% and 9.5%). In Asians, quality of life (QOL) was maintained with no significant differences observed between treatments from baseline in breast cancer-specific QOL and general health status scores. Change from baseline in EuroQol five dimensions index scores was significantly higher with palbociclib plus letrozole (0.013 v -0.069; P = .0132). Geometric mean palbociclib trough concentration values were higher in Asians versus non-Asians (93.8 v 61.7 ng/mL).

Conclusion: Consistent with the overall study population, the addition of palbociclib to letrozole significantly improved PFS in Asians. Hematologic toxicities were more frequent in Asians versus non-Asians but manageable with early dose modifications while maintaining QOL.

Trial registration: ClinicalTrials.gov NCT01740427.

FIG 1

Investigator-assessed progression-free survival in Asian and non-Asian patients (intention-to-treat population) at the data cutoff dates of (A) February 26, 2016, and (B) May 31, 2017. HR, hazard ratio; LET, letrozole; NE, not estimable; PAL, palbociclib; PCB, placebo.

FIG 2

Investigator-assessed progression-free survival in Asian and non-Asian patients with palbociclib dose reductions (intention-to-treat population). Gray line indicates the median progression-free-survival.

FIG 3

Between-treatment comparison of changes from baseline scores among Asian patients (patient-reported outcome analysis set). FACT-B, Functional Assessment of Cancer Therapy-Breast; FACT-G, Functional Assessment of Cancer Therapy-General; LET, letrozole; PAL, palbociclib; PCB, placebo; TOI, Trial Outcome Index.

FIG A1

Patient disposition. (*) Patients who discontinued palbociclib (PAL) or placebo (PCB) could continue to receive letrozole (LET) alone. AE, adverse event; GDHS, global deterioration of health status; PD, progressive disease.

FIG A2

Individual and geometric mean steady-state palbociclib trough concentration (C_trough) in Asian and non-Asian patients. Analysis included all patients with reported steady-state C_trough data from day 14 of cycles 1 and 2 and under fed conditions at the time of pharmacokinetic sampling, regardless of antacid use. The diamonds represent the geometric mean of within-patient mean values of steady-state C_trough, the circles represent individual of within-patient mean values of steady-state C_trough, and the dashed line represents the arithmetic mean of data from all patients. Box plots provide median and 25%/75% quartiles with whiskers to the last point within 1.5 times the interquartile range.