Randomized Phase II Trial Evaluating Treatment with EGFR-TKI Associated with Antiestrogen in Women with Nonsquamous Advanced-Stage NSCLC: IFCT-1003 LADIE Trial
| Autor: | Philippe Masson, Denis Moro-Sibilot, Isabelle Monnet, Anne-Claire Toffart, Bertrand Mennecier, Didier Debieuvre, E. Amour, Eric Pichon, Fabrice Barlesi, Olivier Molinier, Franck Morin, Patrick Aldo Renault, Anne Madroszyk-Flandin, Séverine Fraboulet, Isabelle Rouquette, Alexis B. Cortot, Pierre Jean Souquet, Virginie Westeel, Sandrine Hiret, Clarisse Audigier-Valette, Julien Mazieres, Benjamin Besse, Gérard Zalcman |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty Lung Neoplasms law.invention 03 medical and health sciences 0302 clinical medicine Gefitinib Randomized controlled trial Estrogen Receptor Modulators law Internal medicine Carcinoma Non-Small-Cell Lung Antineoplastic Combined Chemotherapy Protocols medicine Clinical endpoint Biomarkers Tumor Humans Lung cancer neoplasms Protein Kinase Inhibitors Aged Neoplasm Staging Aged 80 and over Fulvestrant business.industry Middle Aged Antiestrogen medicine.disease Prognosis respiratory tract diseases Clinical trial ErbB Receptors 030104 developmental biology Treatment Outcome 030220 oncology & carcinogenesis Mutation Female Erlotinib business medicine.drug |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 26(13) |
| ISSN: | 1557-3265 |
| Popis: | Purpose: The incidence of lung cancer has dramatically increased in women. Preclinical data have suggested that combining EGFR–tyrosine kinase inhibitor (TKI) with an antiestrogen may overcome resistance to EGFR-TKI. Patients and Methods: The IFCT-1003 LADIE trial was a 2 × 2 arms parallel open-label randomized phase II trial. EGFR-TKI–naïve postmenopausal women with advanced lung cancer were treated with gefitinib (G) versus gefitinib + fulvestrant (G+F) in the EGFR-mutated group (EGFR+) or with erlotinib (E) versus erlotinib + fulvestrant (E+F) in the EGFR wild-type group (EGFR-WT). The primary objective was progression-free survival (PFS) at 3 and 9 months for EGFR-WT and EGFR+ patients. Results: Overall, 204 patients (gefitinib 104 and G+F 100) and 175 patients (erlotinib 87 and E+F 88) were enrolled in the EGFR+ and EGFR-WT cohorts. In the EGFR+ cohort, the primary endpoint was reached, with 58% of the G+F group patients being nonprogressive at 9 months. Adding fulvestrant to gefitinib was not associated with improved PFS (9.9 vs 9.4 months) or overall survival (OS; 22.1 vs 28.6 months). In the EGFR-WT cohort, the primary endpoint was also achieved (33.7% of the patients were nonprogressive at 3 months). Adding fulvestrant to erlotinib was not associated with improved outcome (PFS 1.8 vs 2.0 and OS 10.3 vs 7.3 months). No PFS difference was observed regarding estrogen receptor alpha expression. The tolerance was as expected with no treatment-related death. Conclusions: Adding fulvestrant to EGFR-TKI is feasible, but not associated with prolonged PFS regardless of EGFR status. The lack of benefits while combining fulvestrant to EGFR-TKI does not support its future development in an unselected population. |
| Databáze: | OpenAIRE |
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