Matching-adjusted indirect comparison of PFS and OS comparing ribociclib plus letrozole palbociclib plus letrozole as first-line treatment of HR+/HER2- advanced breast cancer.

Background: Current standard-of-care first-line treatment of patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC) is cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) + endocrine therapy. In the MONALEESA-2 trial, first-line ribociclib + letrozole demonstrated statistically significant overall survival (OS) benefit placebo + letrozole in postmenopausal patients with HR+/HER2- ABC. In the PALOMA-2 trial, first-line palbociclib + letrozole did not show OS benefit placebo + letrozole in a similar patient population. Understanding OS outcomes in the respective trials is critical for treatment decisions; however, there are no head-to-head clinical trial data comparing ribociclib and palbociclib.

Objectives: To conduct a matching-adjusted indirect comparison (MAIC) to compare progression-free survival (PFS) and OS of first-line ribociclib + letrozole versus palbociclib + letrozole in postmenopausal patients with HR+/HER2- ABC.

Design: Letrozole-anchored MAIC using individual patient data from MONALEESA-2 and published summary data from PALOMA-2.

Methods: Using individual data, patients from MONALEESA-2 who matched inclusion criteria from PALOMA-2 were selected, and weighting was conducted to ensure baseline characteristics were similar to those in published aggregated data from PALOMA-2. The Bucher method was used to generate corresponding hazard ratios (HRs).

Results: The final effective sample size compared = 150 (ribociclib) and = 112 (placebo) MONALEESA-2 patients with = 444 (palbociclib) and = 222 (placebo) PALOMA-2 patients. After matching and weighting, patient characteristics were well balanced. MAIC analysis showed a numerical PFS benefit [HR, 0.80; 95% confidence interval (CI), 0.58-1.11; = 0.187] and significant OS benefit (HR, 0.68; 95% CI, 0.48-0.96; = 0.031) with ribociclib + letrozole versus palbociclib + letrozole.

Conclusion: Results of this cross-trial MAIC analysis showed a numerical PFS benefit and significantly greater OS benefit with first-line ribociclib + letrozole palbociclib + letrozole. These results support letrozole + ribociclib as the preferred first-line CDK4/6i for postmenopausal patients with HR+/HER2- ABC.

Trial Registration: NCT01958021; https://www.clinicaltrials.gov/study/NCT01958021 (MONALEESA-2) and NCT01740427; https://clinicaltrials.gov/study/NCT01740427 (PALOMA-2).