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

Abstract

Purpose: The incidence of lung cancer has dramatically increased in women. Preclinical data have suggested that combining EGFR-TKI with an anti-estrogen may overcome resistance to EGFR-TKI. Experimental Design: The IFCT-1003 LADIE trial was a 2x2 arms parallel open-label randomized phase II trial. EGFR-TKI-naïve post-menopausal women with advanced lung cancer were treated with gefitinib (G) vs. G + fulvestrant (G+F) in the EGFR mutated group (EGFR+) or with erlotinib (E) vs. E + 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 and 175 patients 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 non-progressive at 9 months. Adding F to G was not associated with improved PFS (9.9 vs 9.4 months) or OS (22.1 vs 28.6 months). In the EGFR-WT cohort, the primary endpoint was also achieved (33.7% of the patients were non-progressive at 3 months). Adding F to E 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 EGFR status. The lack of benefits while combining fulvestrant to EGFR-TKI does not support its future development in unselected population.