Cancer Management and Research (Nov 2021)

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

  • Fasching PA,
  • Delea TE,
  • Lu YS,
  • De Boer R,
  • Hurvitz SA,
  • Moynahan A,
  • Chandiwana D,
  • Lanoue B,
  • Hu H,
  • Thuerigen A,
  • O'Shaughnessy J

Journal volume & issue
Vol. Volume 13
pp. 8179 – 8189

Abstract

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Peter A Fasching,1 Thomas E Delea,2 Yen-Shen Lu,3 Richard De Boer,4 Sara A Hurvitz,5 Aaron Moynahan,2 David Chandiwana,6 Brad Lanoue,6 Huilin Hu,6 Astrid Thuerigen,7 Joyce O’Shaughnessy8 1University Hospital Erlangen, Comprehensive Cancer Center Erlangen—EMN, Department of Gynecology and Obstetrics, Friedrich-Alexander University Erlangen—Nuremberg, Erlangen, Germany; 2Policy Analysis Inc. (PAI), Brookline, MA, USA; 3National Taiwan University Hospital, Taipei, Taiwan; 4Peter MacCallum Cancer Centre, Victoria, Australia; 5University of California, Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, CA, USA; 6Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 7Novartis Pharma AG, Basel, Switzerland; 8Department of Medical Oncology, Baylor University Medical Center, Texas Oncology and US Oncology Network, Dallas, TX, USACorrespondence: Peter A FaschingUniversity Hospital Erlangen, Comprehensive Cancer Center Erlangen—EMN, Department of Gynecology and Obstetrics, Friedrich-Alexander University Erlangen, Maximiliansplatz 2, Erlangen, 91054, GermanyEmail [email protected]: 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: MONALEESA-3, PALOMA-1, overall survival, CDK4/6 inhibitor

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