François-Clément Bidard1,2, William Jacot3, Nicolas Kiavue1, Sylvain Dureau4, Amir Kadi4, Etienne Brain1, Thomas Bachelot5, Hugues Bourgeois6, Anthony Gonçalves7, Sylvain Ladoire8, Hervé Naman9, Florence Dalenc10, Joseph Gligorov11, Marc Espié12, George Emile13, Jean-Marc Ferrero14, Delphine Loirat15, Sophie Frank15, Luc Cabel1, Véronique Diéras16,17, Laure Cayrefourcq18, Cécile Simondi19, Frédérique Berger4, Catherine Alix-Panabières18, Jean-Yves Pierga15. 1. Department of Medical Oncology, Institut Curie, UVSQ and Paris-Saclay University, Saint-Cloud, France. 2. INSERM Center of Clinical Investigations in Biotherapies of Cancer (CIC-BT) 1428, Paris, France. 3. Department of Medical Oncology, Institut du Cancer de Montpellier (ICM), Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Montpellier University, Montpellier, France. 4. Biometry Unit, Institut Curie, PSL Research University, Paris, France. 5. Department of Medical Oncology, Centre Léon Bérard, Lyon, France. 6. Department of Medical Oncology, Victor Hugo Clinic, Le Mans, France. 7. Department of Medical Oncology, Institut Paoli-Calmettes, CRCM, Aix-Marseille University, Marseille, France. 8. Department of Medical Oncology, Centre Georges François Leclerc, Dijon, France. 9. Department of Medical Oncology, Centre Azuréen de Cancérologie, Mougins, France. 10. Department of Medical Oncology, Institut Claudius Regaud, Toulouse, France. 11. Department of Medical Oncology, Hôpital Tenon, Sorbonne Université, Paris, France. 12. Department of Medical Oncology, Hôpital Saint-Louis, Paris, France. 13. Department of Medical Oncology, Centre François Baclesse, Caen, France. 14. Department of Medical Oncology, Centre Antoine Lacassagne, Nice, France. 15. Department of Medical Oncology, Institut Curie, Université de Paris, Paris, France. 16. Formerly with Department of Medical Oncology, Institut Curie, Paris, France. 17. Now with Department of Medical Oncology, Centre Eugène Marquis, Rennes, France. 18. Laboratory of Rare Human Circulating Cells, University Medical Center of Montpellier, EA 2415, Montpellier University, Montpellier, France. 19. Clinical Research Department, Institut Curie, PSL Research University, Paris, France.
Abstract
IMPORTANCE: The choice between chemotherapy and endocrine therapy as first-line treatment for hormone receptor-positive, ERBB2 (also known as HER2)-negative metastatic breast cancer is usually based on the presence of clinical features associated with a poor prognosis. In this setting, a high circulating tumor cell (CTC) count (≥5 CTCs/7.5 mL) is a strong adverse prognostic factor for overall survival and progression-free survival (PFS). OBJECTIVE: To compare the efficacy of a clinician-driven treatment choice vs a CTC-driven choice for first-line treatment. INTERVENTIONS: In the CTC arm, patients received chemotherapy or endocrine therapy according to the CTC count (chemotherapy if ≥5 CTCs/7.5 mL; endocrine therapy if <5 CTCs/7.5 mL), whereas in the control arm, the choice was left to the investigator. DESIGN, SETTING, AND PARTICIPANTS: In the STIC CTC randomized, open-label, noninferiority phase 3 trial, participants were randomized to a clinician-driven choice of first-line treatment or a CTC count-driven first-line treatment choice. Eligible participants were premenopausal and postmenopausal women 18 years or older diagnosed with hormone receptor-positive, ERBB2-negative metastatic breast cancer. Data were collected at 17 French cancer centers from February 1, 2012, to July 28, 2016, and analyzed June 2019 to October 2019. MAIN OUTCOME AND MEASURES: The primary end point was the investigator-assessed PFS in the per-protocol population, with a noninferiority margin of 1.25 for the 90% CI of the hazard ratio. RESULTS: Among the 755 women in the per-protocol population, the median (range) age was 63 (30-88) years [64 (30-88) years for the 377 patients allocated to the CTC arm and 63 (31-87) years for the 378 patients allocated to the standard arm]; 138 (37%) and 103 (27%) received chemotherapy, respectively. Median PFS was 15.5 months (95% CI, 12.7-17.3) in the CTC arm and 13.9 months (95% CI, 12.2-16.3) in the standard arm. The primary end point was met, with a hazard ratio of 0.94 (90% CI, 0.81-1.09). CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that the CTC count may be a reliable biomarker method for guiding the choice between chemotherapy and endocrine therapy as the first-line treatment in hormone receptor-positive, ERBB2-negative metastatic breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01710605.
IMPORTANCE: The choice between chemotherapy and endocrine therapy as first-line treatment for hormone receptor-positive, ERBB2 (also known as HER2)-negative metastatic breast cancer is usually based on the presence of clinical features associated with a poor prognosis. In this setting, a high circulating tumor cell (CTC) count (≥5 CTCs/7.5 mL) is a strong adverse prognostic factor for overall survival and progression-free survival (PFS). OBJECTIVE: To compare the efficacy of a clinician-driven treatment choice vs a CTC-driven choice for first-line treatment. INTERVENTIONS: In the CTC arm, patients received chemotherapy or endocrine therapy according to the CTC count (chemotherapy if ≥5 CTCs/7.5 mL; endocrine therapy if <5 CTCs/7.5 mL), whereas in the control arm, the choice was left to the investigator. DESIGN, SETTING, AND PARTICIPANTS: In the STIC CTC randomized, open-label, noninferiority phase 3 trial, participants were randomized to a clinician-driven choice of first-line treatment or a CTC count-driven first-line treatment choice. Eligible participants were premenopausal and postmenopausal women 18 years or older diagnosed with hormone receptor-positive, ERBB2-negative metastatic breast cancer. Data were collected at 17 French cancer centers from February 1, 2012, to July 28, 2016, and analyzed June 2019 to October 2019. MAIN OUTCOME AND MEASURES: The primary end point was the investigator-assessed PFS in the per-protocol population, with a noninferiority margin of 1.25 for the 90% CI of the hazard ratio. RESULTS: Among the 755 women in the per-protocol population, the median (range) age was 63 (30-88) years [64 (30-88) years for the 377 patients allocated to the CTC arm and 63 (31-87) years for the 378 patients allocated to the standard arm]; 138 (37%) and 103 (27%) received chemotherapy, respectively. Median PFS was 15.5 months (95% CI, 12.7-17.3) in the CTC arm and 13.9 months (95% CI, 12.2-16.3) in the standard arm. The primary end point was met, with a hazard ratio of 0.94 (90% CI, 0.81-1.09). CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that the CTC count may be a reliable biomarker method for guiding the choice between chemotherapy and endocrine therapy as the first-line treatment in hormone receptor-positive, ERBB2-negative metastatic breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01710605.
Authors: Lorenzo Gerratana; Jean-Yves Pierga; James M Reuben; Andrew A Davis; Firas H Wehbe; Luc Dirix; Tanja Fehm; Franco Nolé; Rafael Gisbert-Criado; Dimitrios Mavroudis; Salvatore Grisanti; Jose A Garcia-Saenz; Justin Stebbing; Carlos Caldas; Paola Gazzaniga; Luis Manso; Rita Zamarchi; Marta Bonotto; Angela Fernandez de Lascoiti; Leticia De Mattos-Arruda; Michail Ignatiadis; Maria-Teresa Sandri; Daniele Generali; Carmine De Angelis; Sarah-Jane Dawson; Wolfgang Janni; Vicente Carañana; Sabine Riethdorf; Erich-Franz Solomayer; Fabio Puglisi; Mario Giuliano; Klaus Pantel; François-Clément Bidard; Massimo Cristofanilli Journal: Oncologist Date: 2022-07-05 Impact factor: 5.837
Authors: Costanza Paoletti; Meredith M Regan; Samuel M Niman; Emily M Dolce; Elizabeth P Darga; Minetta C Liu; P Kelly Marcom; Lowell L Hart; John W Smith; Karen L Tedesco; Eitan Amir; Ian E Krop; Angela M DeMichele; Pamela J Goodwin; Margaret Block; Kimberly Aung; Martha E Brown; Robert T McCormack; Daniel F Hayes Journal: NPJ Breast Cancer Date: 2021-06-11