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. 2019 Oct 26;11(11):1661.
doi: 10.3390/cancers11111661.

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  1 , Paola Berchialla  2 , Diana Giannarelli  3 , Cecilia Nisticò  4 , Gianluigi Ferretti  4 , Simona Gasparro  4 , Michelangelo Russillo  4 , Giovanna Catania  4 , Leonardo Vigna  1 , Rossella Letizia Mancusi  5 , Emilio Bria  6   7 , Filippo Montemurro  8 , Francesco Cognetti  9 , Alessandra Fabi  4
Affiliations

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 et al. Cancers (Basel). .

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.

Keywords: abemaciclib; aromatase inhibitors; fulvestrant; metastatic breast cancer; palbociclib; ribociclib.

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Conflict of interest statement

E.B. received honoraria or speakers’ fee from MSD, Astra-Zeneca, Celgene, Pfizer, Helsinn, Eli-Lilly, BMS, Novartis, and Roche; E.B. is supported by the Associazione Italiana Ricerca Cancro (AIRC grants n. IG 20583). All other authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow chart summarizing the process for the identification of the eligible studies.
Figure 2
Figure 2
The network meta-analysis design: Network plot of the network meta-analysis. AI: Aromatase inhibitor.
Figure 3
Figure 3
Forest plots with direct comparisons against fulvestrant for progression-free survival, objective response rate, and clinical benefit rate. AI: Aromatase inhibitor.
Figure 4
Figure 4
Forest plot on treatment effect for progression-free survival by subgroups in the indirect comparison between CDK 4/6 inhibitors, aromatase inhibitors, and fulvestrant. AI: Aromatase inhibitor; CT: Chemotherapy; ET: Endocrine therapy.
See this image and copyright information in PMC

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