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Randomized Phase II Trial Evaluating Treatment with EGFR-TKI Associated with Antiestrogen in Women with Nonsquamous Advanced-Stage NSCLC: IFCT-1003 LADIE Trial.

Authors
  • Mazieres, Julien1, 2
  • Barlesi, Fabrice2, 3
  • Rouquette, Isabelle4
  • Molinier, Olivier2, 5
  • Besse, Benjamin2, 6
  • Monnet, Isabelle2, 7
  • Audigier-Valette, Clarisse2, 8
  • Toffart, Anne-Claire2, 9
  • Renault, Patrick Aldo2, 10
  • Fraboulet, Séverine2, 11
  • Hiret, Sandrine2, 12
  • Mennecier, Bertrand2, 13
  • Debieuvre, Didier2, 14
  • Westeel, Virginie2, 15
  • Masson, Philippe2, 16
  • Madroszyk-Flandin, Anne2, 17
  • Pichon, Eric2, 18
  • Cortot, Alexis B2, 19
  • Amour, Elodie2
  • Morin, Franck2
  • And 3 more
Type
Published Article
Journal
Clinical Cancer Research
Publisher
American Association for Cancer Research
Publication Date
Jun 30, 2020
Volume
26
Issue
13
Pages
3172–3181
Identifiers
DOI: 10.1158/1078-0432.CCR-19-3056
PMID: 32144133
Source
Medline
Language
English
License
Unknown

Abstract

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. 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. 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. 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. ©2020 American Association for Cancer Research.

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