Should All Patients With HR-Positive HER2-Negative Metastatic Breast Cancer Receive CDK 4/6 Inhibitor As First-Line Based Therapy? A Network Meta-Analysis of Data from the PALOMA 2, MONALEESA 2, MONALEESA 7, MONARCH 3, FALCON, SWOG and FACT Trials

Valentina Rossi, Paola Berchialla, Diana Giannarelli, Cecilia Nisticò, Gianluigi Ferretti, Simona Gasparro, Michelangelo Russillo, Giovanna Catania, Leonardo Vigna, Rossella Letizia Mancusi, Emilio Bria, Filippo Montemurro, Francesco Cognetti, Alessandra Fabi

Research output: Contribution to journalArticle

Abstract

Background: We aim to understand whether all patients with hormonal receptor (HR)-positive (+)/human epidermal growth factor receptor-2 (HER2)-negative (-) metastatic breast cancer (MBC) should receive cyclin D-dependent kinase (CDK) 4/6 inhibitor-based therapy as a first-line approach.

METHODS: A network meta-analysis (NMA) using the Bayesian hierarchical arm-based model, which provides the estimates for various effect sizes, were computed.

RESULTS: First-line treatment options in HR+/HER2- MBC, including CDK 4/6 inhibitors combined with aromatase inhibitors (AIs) or fulvestrant (F), showed a significantly longer progression-free survival (PFS) in comparison with AI monotherapy, with a total of 26% progression risk reduction. In the indirect comparison across the three classes of CDK 4/6 inhibitors and F endocrine-based therapies, the first strategy resulted in longer PFS, regardless of specific CDK 4/6 inhibitor (HR: 0.68; 95% CrI: 0.53-0.87 for palbociclib + AI, HR: 0.65; 95% CrI: 0.53-0.79 for ribociclib + AI, HR: 0.63; 95% CrI: 0.47-0.86 for abemaciclib + AI) and patient's characteristics. Longer PFS was also found in patients with bone-only and soft tissues limited disease treated with CDK 4/6 inhibitors.

CONCLUSIONS: CDK 4/6 inhibitors have similar efficacy when associated with an AI in the first-line treatment of HR+ MBC, and are superior to either F or AI monotherapy, regardless of any other patients or tumor characteristics.

Original languageEnglish
JournalCancers
Volume11
Issue number11
DOIs
Publication statusPublished - Oct 26 2019

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