Adjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG-42/AFT-05/BIG-14-03)

Abstract

Purpose: Palbociclib is a cyclin-dependent kinase 4 and 6 inhibitor approved for advanced breast cancer. In the adjuvant setting, the potential value of adding palbociclib to endocrine therapy for hormone receptor-positive breast cancer has not been confirmed.

Patients and methods: In the prospective, randomized, phase III PALLAS trial, patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer were randomly assigned to receive 2 years of palbociclib (125 mg orally once daily, days 1-21 of a 28-day cycle) with adjuvant endocrine therapy or adjuvant endocrine therapy alone (for at least 5 years). The primary end point of the study was invasive disease-free survival (iDFS); secondary end points were invasive breast cancer-free survival, distant recurrence-free survival, locoregional cancer-free survival, and overall survival.

Results: Among 5,796 patients enrolled at 406 centers in 21 countries worldwide over 3 years, 5,761 were included in the intention-to-treat population. At the final protocol-defined analysis, at a median follow-up of 31 months, iDFS events occurred in 253 of 2,884 (8.8%) patients who received palbociclib plus endocrine therapy and in 263 of 2,877 (9.1%) patients who received endocrine therapy alone, with similar results between the two treatment groups (iDFS at 4 years: 84.2% v 84.5%; hazard ratio, 0.96; CI, 0.81 to 1.14; P = .65). No significant differences were observed for secondary time-to-event end points, and subgroup analyses did not show any differences by subgroup. There were no new safety signals for palbociclib in this trial.

Conclusion: At this final analysis of the PALLAS trial, the addition of adjuvant palbociclib to standard endocrine therapy did not improve outcomes over endocrine therapy alone in patients with early hormone receptor-positive breast cancer.

Trial registration: ClinicalTrials.gov NCT02513394.

FIG 1.

CONSORT diagram. ^aOf 6,688 patients who were screened for eligibility, 892 were not randomly assigned because of the following reasons: not meeting inclusion criteria (n = 466), declined to participate (n = 259), and other reasons (n = 167), leading to 5,796 randomly assigned patients. ^bIncludes 36 patients from the palbociclib plus endocrine therapy group who received endocrine therapy only.

FIG 2.

Kaplan-Meier estimates of survival for the primary end point of (A) iDFS and for the secondary end points of (B) invasive breast cancer–free survival, (C) distant recurrence-free survival, (D) locoregional recurrence-free survival, and (E) OS are shown for women with stage II-III histologically confirmed hormone receptor–positive, HER2-negative breast cancer. The HRs with 95% CIs are given for each end point. In addition, the P value of a stratified log-rank test is shown for the primary end point. The numbers along the curves indicate the event-free rates in yearly intervals. ET, endocrine treatment; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; iDFS, invasive disease-free survival; OS, overall survival; P, palbociclib.

FIG 3.

The forest plot shows the HRs (diamonds) and 95% CIs (horizontal lines) with regard to invasive disease-free survival within subgroups according to anatomic stage, tumor stage (T-stage), nodal status (N-stage), histologic grade, prior neoadjuvant or adjuvant chemotherapy, and age group. The solid vertical line indicates the overall HR estimate, and the dashed vertical line indicates a HR of 1.00. No significant interactions between subgroups and treatment groups were observed. ET, endocrine treatment; HR, hazard ratio; P, palbociclib.