Combined analysis of two Phase II studies evaluating first-line erlotinib in NSCLC with EGFR mutation: JO22903/JO25567

Abstract

Background: First-line erlotinib monotherapy showed good efficacy and safety in two phase II studies; JO22903 (K Goto et al. Lung Cancer 2013) and JO25567 (T Seto et al. Lancet Oncol 2014), in which Japanese NSCLC patients ( pts) with EGFR mutation were recruited. To evaluate erlotinib efficacy and safety more precisely, we conducted a combined analysis of JO22903 and JO25567. Methods: Pts receiving erlotinib monotherapy in JO22903 and JO25567 were included. Stage IIIB/IV or recurrent NSCLC with EGFR activating mutation, ECOG PS 0-1, without previous chemotherapy were eligible in both studies. T790M mutation, squamous cell carcinoma and brain metastases (BM) were ineligible in JO25567. Eligible pts received oral erlotinib 150 mg daily until PD or unacceptable toxicity. Primary endpoint was PFS. We conducted exploratory subgroup analysis and evaluated PD pattern, focusing on brain as major PD site in pts who were treated with EGFR-TKI (Omuro AM et al. Cancer 2005). Results: The combined analysis included 178 pts as safety population: 101 from JO22903 (2 with T790M mutation were excluded) and 77 who were randomized to erlotinib monotherapy arm from JO25567. Of the safety population, 177 pts were eligible for efficacy analysis. Median PFS was 10.9 months (95% CI: 9.7-12.5). The safety profile was as previously reported in each study: rash (any grade; 99%, grade 3 < ; 19%) and diarrhea (any grade; 79%, grade 3 < ; 1%) were most common. In a subgroup analysis by age, median PFS was 10.9 months for pts aged <75 years (n = 148) and 10.3 months for pts aged >75 years (n = 29). Safety profile seemed to be similar between age groups. Regarding PD pattern, progression of brain lesions were observed in 6 (4.8%) of 125 pts who had PD: Two pts had BM at baseline and 4 pts who had no BM at base line. Conclusions: This combined analysis showed good efficacy and safety of erlotinib in Japanese pts with EGFR mutation. Brain lesions seemed to be well controlled by erlotinib