Matching-Adjusted Indirect Comparison of Ribociclib Plus Fulvestrant versus Palbociclib Plus Letrozole as First-Line Treatment of HR+/HER2- Advanced Breast Cancer

Peter A Fasching; Thomas E Delea; Yen-Shen Lu; Richard De Boer; Sara A Hurvitz; Aaron Moynahan; David Chandiwana; Brad Lanoue; Huilin Hu; Astrid Thuerigen; Joyce O'Shaughnessy

doi:10.2147/CMAR.S325043

Matching-Adjusted Indirect Comparison of Ribociclib Plus Fulvestrant versus Palbociclib Plus Letrozole as First-Line Treatment of HR+/HER2- Advanced Breast Cancer

Cancer Manag Res. 2021 Nov 1:13:8179-8189. doi: 10.2147/CMAR.S325043. eCollection 2021.

Authors

Affiliations

¹ University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Department of Gynecology and Obstetrics, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany.
² Policy Analysis Inc. (PAI), Brookline, MA, USA.
³ National Taiwan University Hospital, Taipei, Taiwan.
⁴ Peter MacCallum Cancer Centre, Victoria, Australia.
⁵ University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA.
⁶ Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
⁷ Novartis Pharma AG, Basel, Switzerland.
⁸ Department of Medical Oncology, Baylor University Medical Center, Texas Oncology and US Oncology Network, Dallas, TX, USA.

Abstract

Purpose: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) plus endocrine therapy are recommended for first-line treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). However, not all CDK4/6i trials have reported significant overall survival (OS) benefit, and there have been no head-to-head trials. Two trials have reported OS outcomes in first-line patients: MONALEESA-3 reported significant OS benefit with first- or second-line ribociclib plus fulvestrant (RIB+FUL) versus placebo plus fulvestrant (PBO+FUL), while PALOMA-1 reported no significant OS benefit for palbociclib plus letrozole (PAL+LET) versus LET in first-line postmenopausal patients. Matched-adjusted indirect comparisons (MAICs) are an established method for comparing efficacy of treatments from different trials. We used an MAIC to compare first-line patients from MONALEESA-3 and PALOMA-1.

Patients and methods: An unanchored MAIC of progression-free survival (PFS) and OS in first-line patients with HR+/HER2- ABC treated with RIB+FUL versus PAL+LET was conducted using individual patient data from MONALEESA-3 and aggregated data from PALOMA-1. To match patients in PALOMA-1, patients in MONALEESA-3 were limited to those with no prior endocrine therapy for ABC and no (neo) adjuvant LET ≤12 months before enrollment. PFS and OS were compared using Kaplan-Meier estimators and Cox regression.

Results: A total of 329 and 178 patients from RIB+FUL and PBO+FUL arms, respectively, of MONALEESA-3 were matched to 84 and 81 patients from PAL+LET and LET arms of PALOMA-1. After weighting, OS was significantly longer for RIB+FUL versus PAL+LET (hazard ratio [HR], 0.50; 95% CI, 0.32-0.77; p = 0.0020). PFS favored RIB+FUL versus PAL+LET, although the difference was not statistically significant (HR, 0.77; 95% CI, 0.54-1.10; p = 0.1553).

Conclusion: Using MAIC to adjust for trial differences, OS comparisons favored RIB+FUL over PAL+LET as first-line treatment in postmenopausal patients with HR+/HER2- ABC. These exploratory results suggest a significant increase in OS benefit with RIB treatment compared with PAL.

Keywords: CDK4/6 inhibitor; MONALEESA-3; PALOMA-1; overall survival.

Grants and funding

The financial support for this study was provided by Novartis.