Overall Survival With Palbociclib Plus Letrozole in Advanced Breast Cancer

Abstract

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.PALOMA-2 demonstrated statistically and clinically significant improvement in progression-free survival with palbociclib plus letrozole versus placebo plus letrozole in estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced breast cancer (ABC). Here, we report results for the secondary end point overall survival (OS). Postmenopausal women (N = 666) with ER+/HER2- ABC without previous systemic therapy for ABC were randomly assigned 2:1 to palbociclib plus letrozole or placebo plus letrozole. After a median follow-up of 90.1 months, 405 deaths were observed and 155 patients were known to be alive. The median OS was 53.9 months (95% CI, 49.8 to 60.8) with palbociclib plus letrozole versus 51.2 months (95% CI, 43.7 to 58.9) with placebo plus letrozole (hazard ratio [HR], 0.96 [95% CI, 0.78 to 1.18]; stratified one-sided P = .34). An imbalance in the number of patients with unknown survival outcome between the treatment arms (13.3% v 21.2%, respectively) limited interpretation of OS results. With recovered survival data, the median OS was 53.8 (95% CI, 49.8 to 59.2) versus 49.8 months (95% CI, 42.3 to 56.4), respectively (HR, 0.92 [95% CI, 0.76 to 1.12]; one-sided P = .21). OS was not significantly improved with palbociclib plus letrozole compared with placebo plus letrozole.

Trial registration: ClinicalTrials.gov NCT01740427.

FIG 1.

OS in the ITT population and by subgroup. (A) Kaplan-Meier curve of OS in the ITT population. (B) Forest plot of OS by subgroup. (C) Kaplan-Meier curve of OS in the ITT population after recovery of data. (D) Forest plot of OS by subgroup after recovery of data. ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; ITT, intent-to-treat; LET, letrozole; NE, not estimable; OS, overall survival; PAL, palbociclib; PBO, placebo.

FIG 2.

OS and time to chemotherapy. (A) Kaplan-Meier curve of OS in the ITT populations of both PALOMA-1 and PALOMA-2. Control arm was LET alone in PALOMA-1and PBO plus LET in PALOMA-2. Kaplan-Meier curve (B) for time to first subsequent chemotherapy and (C) after censoring for deaths without chemotherapy. HR, hazard ratio; ITT, intent-to-treat; LET, letrozole; OS, overall survival; PAL, palbociclib; PBO, placebo; TTC, time to chemotherapy.