Phase I/II study of erlotinib plus S-1 for patients with previously treated non-small cell lung cancer: Thoracic Oncology Research Group (TORG) 0808/0913

• Published in: Investigational new drugs Vol. 39; no. 1; pp. 202 - 209
• Main Authors: Nakahara, Yoshiro, Shimokawa, Tsuneo, Misumi, Yuki, Nogami, Naoyuki, Shinkai, Tetsu, Seki, Nobuhiko, Hosomi, Yukio, Hida, Naoya, Okamoto, Hiroaki
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.02.2021; Springer Nature B.V
• Subjects: Anticancer properties; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Antitumor activity; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Combination therapy; Disease control; Dosage; Dose-Response Relationship, Drug; Drug Combinations; Enrollments; Enzyme inhibitors; Epidermal growth factor; Epidermal growth factor receptors; ErbB Receptors - genetics; Erlotinib Hydrochloride - administration & dosage; Erlotinib Hydrochloride - adverse effects; Erlotinib Hydrochloride - therapeutic use; Growth factors; Humans; Inhibitor drugs; Kinases; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Medicine; Medicine & Public Health; Mutation; Neoplasm Staging; Non-small cell lung carcinoma; Oncology; Oxonic Acid - administration & dosage; Oxonic Acid - adverse effects; Oxonic Acid - therapeutic use; Pharmacology/Toxicology; Phase II Studies; Protein-tyrosine kinase; Small cell lung carcinoma; Targeted cancer therapy; Tegafur - administration & dosage; Tegafur - adverse effects; Tegafur - therapeutic use; Thorax; Toxicity; Tyrosine; Epidermal growth factor receptor tyrosine kinase inhibitor; Erlotinib; S-1; Non-small cell lung cancer
• ISSN: 0167-6997; 1573-0646; 1573-0646
• DOI: 10.1007/s10637-020-00985-4

Summary Introduction In preclinical data, the combination therapy with S-1 and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) had a synergistic antitumor effect on non-small cell lung cancer (NSCLC), regardless of the EGFR mutation status. Patients and Methods Patients with previously treated NSCLC and adequate organ function regardless of EGFR mutation status were eligible for the phase I study, with wild-type EGFR were eligible for the phase II study. Treatment consisted of erlotinib 150 mg/body orally once every day and S-1 60 mg/m 2 , 70 mg/m 2 , or 80 mg/m 2 (level 0, level 1, or level 2) orally on days 1–14 every three weeks. The primary endpoint for the phase I study was the determination of the recommended dose (RD), the phase II study was the overall response rate (ORR). Results A total of 7 patients with performance-status (PS) 0 or 1 were enrolled as subjects in phase I. Five of these subjects were EGFR-mutation positive. Four subjects were enrolled at S-1 dose level 1 and 3 were enrolled at S-1 dose level 2. No dose-limiting toxicities were observed in these subjects. The RD was decided as erlotinib 150 mg/body and S-1 80 mg/m 2 . In phase I, 5 subjects achieved partial response, and the ORR was 71.4%. A total of 10 patients with PS 0, 1, or 2 EGFR-wild type NSCLC were enrolled in phase II. In phase II, the ORR was 10.0%, and the disease control rate (DCR) was 40.0%. After the enrollment of 10 subjects, enrollment was stopped based on two treatment-related deaths. Conclusion The combination therapy of erlotinib plus S-1 was not feasible in the EGFR wild-type NSCLC at least and early stopped. Trial registration: UMIN-CTR Identifier: 000003421 (2010/03/31, phase I), 000003422 (2010/03/31, Phase II).