- Phase 2 data show no survival benefit for adding fulvestrant to gefitinib in women with NSCLC.
- A phase 3 trial is not warranted.
Why this matters
- Incidence of lung cancer is increasing dramatically in women.
- The preferential involvement of the endothelial growth factor receptor (EGFR) pathway has been identified.
- Hormonal factors may be influential in women with NSCLC.
- Preclinical data have shown that the combination of an EGFR-tyrosine kinase inhibitor (TKI) with an anti-estrogen could overcome resistance to EGFR-TKI.
- 2×2 groups, parallel, open-label, randomized, phase 2 trial.
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2 postmenopausal women with advanced-stage lung adenocarcinoma.
- Treatment for women with EGFR mutations (n=204): gefitinib (250 mg/day, n=104) vs gefitinib+fulvestrant 500 mg/month (n=100) and supplementary combined dose at day 15 in first- or second-line setting.
- Treatment for women with EGFR wild-type (n=175): either erlotinib (150 mg/day, n=87) or erlotinib+fulvestrant (n=88) in second- or third-line setting.
- Treatment until disease progression or unacceptable toxicity.
- Primary objective: PFS at 3 months for EGFR wild-type patients and 9 months for those with EGFR-sensitive mutations.
- Funding: IFCT-1003 LADIE Trial: AstraZeneca; Roche; French League Against Cancer.
- Study groups were balanced at baseline for age, sex, smoking history, ECOG PS, clinical stage, and prevalence of adenocarcinoma.
- Median number of fulvestrant injections: 10 in the gefitinib+fulvestrant group, 3 in the erlotinib+fulvestrant group.
- Tolerance to treatment was similar whether or not fulvestrant was included.
- In patients with EGFR-sensitive mutations, the addition of fulvestrant to treatment with either gefitinib or erlotinib was not associated with significantly better PFS at 9 months (median PFS for gefitinib and gefitinib fulvestrant: 10.9 [8.8-13.2] and 9.4 [7.7-11.0] months, respectively), or with OS at 3 months (median OS: 29.9 [24.2-43.8] and 22.1 [18.6-25.7] months, respectively).
- In EGFR wild-type patients, a similar pattern was evident, with no PFS or OS benefit observed with the addition of fulvestrant.