Randomized Phase II Trial Evaluating Treatment with EGFR-TKI Associated with Antiestrogen in Women with Nonsquamous Advanced-Stage NSCLC: IFCT-1003 LADIE Trial
2 IFCT - Intergroupe Francophone de Cancérologie Thoracique [Paris]
3 CRCM - Centre de Recherche en Cancérologie de Marseille
4 APHM - Assistance Publique - Hôpitaux de Marseille
5 Service Anatomie et cytologie pathologiques [CHU Toulouse]
6 Service de pneumologie et oncologie thoracique [CH Le Mans]
7 IGR - Institut Gustave Roussy
8 CHI Créteil
9 Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse
10 Hôpital Michallon
11 IAB - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
12 Centre hospitalier de Pau
13 Hôpital Foch [Suresnes]
14 ICO-René Gauducheau Cancer Center
15 Nouvel Hôpital Civil de Strasbourg
16 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
17 Groupe hospitalier de la région de Mulhouse et Sud-Alsace
18 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
19 URePSSS - Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - ULR 7369 - ULR 4488
20 IPC - Institut Paoli-Calmettes
21 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
22 CANTHER - Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277
23 IRESNE - Institut de recherche sur les systèmes nucléaires pour la production d'énergie bas carbone (CEA - DES)
24 UPCité - Université Paris Cité
25 CIC 1425 - Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique
26 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
- Fonction : Auteur
- PersonId : 1033301
- ORCID : 0000-0002-5921-7613
- Fonction : Auteur
- PersonId : 1477223
- IdHAL : atoffart
- ORCID : 0000-0003-4377-0227
- Fonction : Auteur
- PersonId : 1212267
- ORCID : 0000-0003-0098-2238
Résumé
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 Â 2 arms parallel open-label randomized phase II trial. EGFR-TKI-na€ ve postmenopausal women with advanced lung cancer were treated with gefitinib (G) versus gefitinib þ fulvestrant (GþF) in the EGFR-mutated group (EGFR þ ) or with erlotinib (E) versus erlotinib þ fulvestrant (EþF) 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 þ patients.
Results: Overall, 204 patients (gefitinib 104 and GþF 100) and 175 patients (erlotinib 87 and EþF 88) were enrolled in the EGFR þ and EGFR-WT cohorts. In the EGFR þ cohort, the primary endpoint was reached, with 58% of the GþF 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 treatmentrelated 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.