228MO - PALOMA-4: Primary results from a phase III trial of palbociclib (PAL) + letrozole (LET) vs placebo (PBO) + LET in Asian postmenopausal women with estrogen receptor–positive/human epidermal growth factor receptor 2–negative (ER+/HER2–) advanced breast cancer (ABC)

Background

The incidence of breast cancer in Asian women has increased rapidly over the past 40 years. A previous subgroup analysis from PALOMA-2 indicated that PAL + LET may be effective as first-line therapy in postmenopausal Asian women with ER+/HER2– ABC. The PALOMA-4 study assessed the efficacy and safety of PAL + LET in Asian patients (pts).

Methods

PALOMA-4, an international, double-blind, phase 3 trial, randomized postmenopausal Asian women who had not received prior systemic therapy for ER+/HER2– ABC 1:1 to receive PAL (125 mg/d orally; 3 weeks on, 1 week off) + LET (2.5 mg/d orally; continuously) or PBO + LET. The primary endpoint was Kaplan-Meier analysis of investigator-assessed progression-free survival (PFS); between-arms comparisons used a stratified log-rank test. Secondary endpoints included objective response rate (ORR) and safety; between-arms comparisons used the Cochran-Mantel-Haenszel test. Safety was summarized descriptively.

Results

Pts (N=340) were randomized (PAL + LET, 169; PBO + LET, 171). The median duration of follow-up for overall survival was 52.8 mo. Baseline characteristics were generally similar between the 2 groups. At the data cutoff (Aug 31, 2020), the median PFS based on investigator assessment was 21.5 mo for PAL + LET and 13.9 mo for PBO + LET (hazard ratio, 0.68 [95% CI, 0.53–0.87]; P=0.0012). The ORR based on investigator assessment was 37.3% vs 31.6%, respectively, among all pts (P=0.154) and 43.4% vs 38.0% in pts with measurable disease (P=0.206). The most common grade 3/4 adverse events (AEs) with PAL + LET vs PBO + LET were neutropenia (84.5% vs 1.2%), leukopenia (36.3% vs 0.6%), thrombocytopenia (6.5% vs 0.6%), and anemia (4.8% vs 1.8%). Febrile neutropenia was reported only with PAL + LET (2.4 %). The discontinuation rate due to AEs was 7.7% with PAL + LET and 2.9% with PBO + LET.

Conclusions

PALOMA-4, the largest study to date of a cyclin-dependent kinase 4/6 inhibitor in Asian pts with ABC, confirmed the efficacy and safety of PAL + LET as first-line therapy in postmenopausal Asian women with ER+/HER2– ABC.

Clinical trial identification

NCT02297438.

Editorial acknowledgement

Editorial support was provided by Anny Wu, PharmD, of ICON plc (North Wales, PA, USA) and was funded by Pfizer Inc.

Legal entity responsible for the study

Pfizer Inc.

Funding

Pfizer Inc.

Disclosure

B. Xu: Financial Interests, Personal, Advisory Role, Consultancy: Novartis, Roche; Financial Interests, Institutional, Research Grant: Hengrui; Financial Interests, Institutional, Funding: Hengrui; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Pfizer, Roche, Eisai. C. Huang: Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, Novartis, Pfizer, Roche; Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, Daiichi Sankyo, EirGenix, Lilly, MSD, Novartis, OBI, Pfizer, Roche; Financial Interests, Institutional, Funding: Amgen, AstraZeneca, Daiichi Sankyo, EirGenix, Lilly, MSD, Novartis, OBI, Pfizer, Roche; Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Lilly, Novartis, Pfizer, Roche; Financial Interests, Personal, Other, Consultancy: Amgen, AstraZeneca, Lilly, Novartis, Pfizer, Roche; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Amgen, Pfizer, Roche. V. Sriuranpong: Financial Interests, Institutional, Research Grant: Roche, MSD, Novartis, Pfizer, AstraZeneca; Financial Interests, Institutional, Funding: Roche, MSD, Novartis, Pfizer, AstraZeneca; Financial Interests, Personal, Advisory Role: Roche, Novartis, Boehringer Ingelheim, MSD, Pfizer, Amgen; Financial Interests, Personal, Other, Consultancy: Roche, Novartis, Boehringer Ingelheim, MSD, Pfizer, Amgen. K.C.R. Ngan: Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Personal, Advisory Role: Pfizer, Novartis, Sanofi, AstraZeneca, Lilly, MSD, Zai Lab, Roche, Eisai; Financial Interests, Personal, Other, Consultancy: Pfizer, Novartis, Sanofi, AstraZeneca, Lilly, MSD, Zai Lab, Roche, Eisai; Financial Interests, Personal, Speaker’s Bureau: Novartis, AstraZeneca, Sanofi, Pfizer, Zai Lab, Eisai, Lilly, MSD; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer, Astellas, Novartis, MSD, Roche, Eisai, Merck, Sanofi, BMS, Zai Lab. X. Wang: Financial Interests, Personal, Full or part-time Employment: Pfizer; Financial Interests, Personal, Stocks/Shares: Pfizer. H. Zhao: Financial Interests, Personal, Full or part-time Employment: Pfizer. All other authors have declared no conflicts of interest.