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Lactate Dehydrogenase (LDH) Response to First-Line Treatment Predicts Survival in Metastatic Breast Cancer: First Clues for a Cost-Effective and Dynamic Biomarker
Article

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

1
Breast Unit, S. Camillo-Forlanini Hospital of Rome, 00152 Rome, Italy
2
Department of Clinical and Biological Sciences, University of Turin, 10124 Turin, Italy
3
Department of Medical Statistics, IRCCS Regina Elena National Cancer Institute, 00128 Rome, Italy
4
Division of Medical Oncology1, IRCCS Regina Elena National Cancer Institute, 00128 Rome, Italy
5
Department of Statistical Sciences, University Tor Vergata of Rome, 00133 Rome, Italy
6
Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
7
Department of Medical Oncology, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
8
Direzione Day Hospital Oncologico Multidisciplinare, Istituto di Candiolo, FPO-IRCCS, 10060 Candiolo, Italy
9
Università La Sapienza, 00185 Rome, Italy
*
Author to whom correspondence should be addressed.
These authors equally contributed to the statistical analysis.
Cancers 2019, 11(11), 1661; https://doi.org/10.3390/cancers11111661
Received: 25 September 2019 / Revised: 21 October 2019 / Accepted: 22 October 2019 / Published: 26 October 2019
(This article belongs to the Special Issue Treatment Strategies and Survival Outcomes in Breast Cancer)
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. View Full-Text
Keywords: palbociclib; ribociclib; abemaciclib; fulvestrant; aromatase inhibitors; metastatic breast cancer palbociclib; ribociclib; abemaciclib; fulvestrant; aromatase inhibitors; metastatic breast cancer
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MDPI and ACS Style

Rossi, V.; Berchialla, P.; Giannarelli, D.; Nisticò, C.; Ferretti, G.; Gasparro, S.; Russillo, M.; Catania, G.; Vigna, L.; Mancusi, R.L.; Bria, E.; Montemurro, F.; Cognetti, F.; Fabi, A. 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. Cancers 2019, 11, 1661. https://doi.org/10.3390/cancers11111661

AMA Style

Rossi V, Berchialla P, Giannarelli D, Nisticò C, Ferretti G, Gasparro S, Russillo M, Catania G, Vigna L, Mancusi RL, Bria E, Montemurro F, Cognetti F, Fabi A. 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. Cancers. 2019; 11(11):1661. https://doi.org/10.3390/cancers11111661

Chicago/Turabian Style

Rossi, Valentina, Paola Berchialla, Diana Giannarelli, Cecilia Nisticò, Gianluigi Ferretti, Simona Gasparro, Michelangelo Russillo, Giovanna Catania, Leonardo Vigna, Rossella L. Mancusi, Emilio Bria, Filippo Montemurro, Francesco Cognetti, and Alessandra Fabi. 2019. "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" Cancers 11, no. 11: 1661. https://doi.org/10.3390/cancers11111661

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