Paloma-4: Primary Results From A Phase Iii Trial Of Palbociclib (Pal) Plus Letrozole (Let) Vs Placebo (Pbo) Plus Let In Asian Postmenopausal Women With Estrogen Receptore Positive/Human Epidermal Growth Factor Receptor 2-Negative (Er+/Her2-) Advanced Breast Cancer (Abc)

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). 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. 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. 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.