A randomized phase II trial of erlotinib vs. S-1 as a third- or fourth-line therapy for patients with wild-type EGFR non-small cell lung cancer (HOT1002)

Purpose A high proportion of patients with wild-type EGFR non-small cell lung cancer (NSCLC) receive third-line therapy and beyond, with no prospective randomized trials addressing the issue. This study aimed to select the most suitable regimen as a third- or fourth-line therapy for wild-type EGFR NSCLC. Methods This multicenter, randomized phase II study in Japan included patients with recurrent or advanced NSCLC with wild-type or unknown EGFR , who progressed after two or three previous chemotherapies. The patients were randomly assigned to erlotinib (150 mg/day, days 1–21) or S-1 (80–120 mg/day, days 1–14) every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was disease control rate (DCR). The secondary endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), toxicity, and quality of life (QOL). Results From 2011 to 2016, 37 patients were randomly assigned to receive erlotinib (E arm, n = 19) and S-1 (S arm, n = 18). This study was terminated prematurely because of poor patient accrual. DCR/ORR were 42.1%/15.8% in the E arm and 66.7%/16.7% in the S arm. Median PFS/OS were 1.6 months/8.0 months in the E arm and 3.3 months/12.2 months in the S arm. In both groups, the most commonly reported grade 3–4 toxicities were fatigue, anorexia, and nausea. One grade 5 pneumonitis occurred in the S arm. No significant difference was seen in QOL. Conclusions S-1 as a third- or fourth-line therapy for wild-type EGFR NSCLC showed numerically better clinical outcomes than erlotinib. Clinical trial registration no. UMIN000005308.