Efficacy, tolerability, and outcomes of generic palbociclib in metastatic HR-positive, HER2-negative breast cancer: An ambispective study from a tertiary cancer center in South India.

Abstract

e13034 Background: CDK4/6 inhibitors have transformed outcomes in hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (MBC). In India, generic palbociclib has markedly improved accessibility at approximately 5–10% of the cost of the innovator formulation (INR 5,000–8,000 vs INR 95,000 per month), yet real-world data are limited. We evaluated indications, tolerability, and survival outcomes of generic palbociclib + endocrine therapy (ET) at a tertiary oncology center. Methods: Ambispective cohort study (Department of Medical Oncology, Amala Institute of Medical Sciences, Kerala). Retrospective: January 2022–June 2024; prospective: July 2024–September 2025. Only one patient initiated palbociclib in 2022 (switched to generic formulation in 2023); all others received generic palbociclib from treatment start. Adults with HR-positive, HER2-negative MBC receiving generic palbociclib + ET were eligible. Primary endpoints: treatment patterns, tolerability, dose modifications. Secondary endpoints: progression-free survival (PFS), overall survival (OS), objective response rate. Kaplan-Meier estimates and Cox regression were used. Results: Ninety-seven patients (median age 59 years [IQR 53–69]; 82.5% postmenopausal; 72.2% ECOG 1). Palbociclib was first-line in 63.9% and second-line in 27.8%; endocrine partner letrozole 79.4%, fulvestrant 15.5%. Starting dose: 125 mg (22.7%), 100 mg (50.5%), 75 mg (26.8%). Median follow-up 16 months; 31 progressions (32%) and 22 deaths (22.7%) occurred. Median PFS and OS not reached. One-year PFS 74.3% (95% CI 65.3–84.6); one-year OS 87.0% (95% CI 80.1–94.5). Neutropenia (any grade) 93.8% (grade 3–4 ,19.6%); non-hematologic grade ≥3 events <2%. Multivariate analysis: ECOG 3 (HR 9.27, P=0.042) and second-line use (HR 4.95, P<0.001) independently predicted inferior PFS; similar trends for OS. ER Allred score ≤4 trended toward poorer outcome (P=0.055). Conclusions: Generic palbociclib combined with ET demonstrated favorable efficacy and manageable tolerability in HR-positive, HER2-negative MBC, with outcomes comparable to global registration trials despite frequent upfront dose reductions and at >90% lower drug acquisition cost versus the originator. Poor performance status, later-line use, and low ER expression were associated with inferior survival. These findings strongly support the real-world effectiveness and value of generic palbociclib in resource-constrained settings; larger multicenter studies with longer follow-up are warranted.