Phase II study of S-1 and irinotecan combination therapy in EGFR-mutated non-small cell lung cancer resistant to epidermal growth factor receptor tyrosine kinase inhibitor: North Japan Lung Cancer Study Group Trial 0804 (NJLCG0804).

We conducted a multicenter phase II trial to evaluate the efficacy and safety of S-1 and irinotecan combination therapy in patients with epidermal growth factor receptor-mutated non-small-cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors. Epidermal growth factor receptor-mutated non-small-cell lung cancer patients treated with epidermal growth factor receptor tyrosine kinase inhibitors and platinum-based chemotherapy received 80 mg/m 2 S-1 on days 1-14 and 70 mg/m 2 irinotecan on days 1 and 8 of a 21-day cycle. The primary endpoint was disease control rate 8 weeks after enrollment. The secondary endpoints were progression-free survival, overall response rate, and safety. We enrolled 25 patients from five hospitals. The patients underwent a median of four cycles. The disease control rate, 8 weeks after enrollment, was 84% (95% confidence interval 63.9-95.5%). Progression-free survival and overall survival were 5.0 and 17.1 months, respectively. The overall response rate was 52.0%. Grade ≥ 3 adverse events were reported in 56.0% of patients: hematological toxicities of leukopenia (44%), neutropenia (52%), anemia (20%), thrombocytopenia (20%), and febrile neutropenia (16%). Non-hematological toxicities of grade ≥ 3 included elevated alanine aminotransferase (4%), anorexia (8%), nausea (4%), diarrhea (16%), and pulmonary embolism (4%). None developed grade 5 toxicities. Combination therapy with S-1 and irinotecan in patients with epidermal growth factor receptor-mutated non-small-cell lung cancer treated with epidermal growth factor receptor tyrosine kinase inhibitors and platinum-based chemotherapy demonstrated high effectiveness with tolerable toxicities. Future phase III studies are needed to evaluate the role of this treatment in such patients.