RESUMO
OBJECTIVES: This open-label, randomized phase II trial evaluated antitumor efficacy of an antiestrogen, fulvestrant, in combination with human epidermal growth factor receptor (EGFR) inhibitor, erlotinib, in advanced non-small cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: Patients with advanced or metastatic NSCLC, ECOG 0-2, previous chemotherapy unless patient refusal, and no prior EGFR-directed therapy were randomized 2:1 to erlotinib 150â¯mg oral daily plus 500â¯mg intramuscular fulvestrant on day 1, 15, 29 and every 28 days thereafter or erlotinib alone 150â¯mg oral daily. The primary end point was objective response rate (ORR); secondary endpoints included progression free survival (PFS) and overall survival (OS). RESULTS: Among 106 randomized patients, 100 received at least one dose of study drug. ORR was 16.4% (11 of 67 patients) for the combination versus 12.1% (4 of 33 patients) for erlotinib (pâ¯=â¯0.77). PFS median 3.5 versus 1.9 months [HRâ¯=â¯0.86, 95% CI (0.52-1.43), pâ¯=â¯0.29] and OS median 9.5 versus 5.8 months [HRâ¯=â¯0.92, 95% CI (0.57-1.48), pâ¯=â¯0.74] numerically favored the combination. In an unplanned subset analysis, among EGFR wild type patients (nâ¯=â¯51), but not EGFR mutant patients (nâ¯=â¯17), median PFS was 3.5 versus 1.7 months [HRâ¯=â¯0.35, 95% CI (0.14-0.86), pâ¯=â¯0.02] and OS was 6.2 versus 5.2 months [HRâ¯=â¯0.72, 95% CI (0.35-1.48), pâ¯=â¯0.37] for combined therapy versus erlotinib, respectively. Notably, EGFR WT patients were more likely to be hormone receptor-positive (either estrogen receptor α- and/or progesterone receptor-positive) compared to EGFR mutant patients (50% versus 9.1%, respectively) (pâ¯=â¯0.03). Treatment was well tolerated with predominant grade 1-2 dermatologic and gastrointestinal adverse effects. CONCLUSION: Addition of fulvestrant to erlotinib was well tolerated, with increased activity noted among EGFR wild type patients compared to erlotinib alone, albeit in an unplanned subset analysis.
