Yasuyuki Ikezawa1,2, Hajime Asahina3, Satoshi Oizumi1,4, Masahiro Watanabe4, Kei Takamura5, Yasutaka Kawai2, Noriyuki Yamada4,6, Toshiyuki Harada7, Ichiro Kinoshita8, Yuka Fujita9, Eisaku Miyauchi10, Takahiro Ogi5, Toraji Amano8, Megumi Furuta1, Jun Sakakibara-Konishi1, Hiroshi Nishihara11, Hirotoshi Dosaka-Akita8, Hiroshi Isobe12, Masaharu Nishimura1. 1. First Department of Medicine, Hokkaido University Hospital, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan. 2. Department of Respiratory Medicine, Oji General Hospital, 3-4-8 Wakakusa-cho, Tomakomai, Hokkaido, 053-8506, Japan. 3. First Department of Medicine, Hokkaido University Hospital, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan. asahinah@pop.med.hokudai.ac.jp. 4. Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center, 2-3-54 Kikusui 4, Shiroishi-ku, Sapporo, Hokkaido, 003-0804, Japan. 5. Department of Respiratory Medicine, Obihiro-Kosei General Hospital, 1 West 6, North 8, Obihiro, Hokkaido, 080-0016, Japan. 6. Department of Respiratory Medicine, Iwamizawa Municipal General Hospital, 2 West 7, 9-jo, Iwamizawa, Hokkaido, 068-8555, Japan. 7. Center for Respiratory Diseases, JCHO Hokkaido Hospital, 3-18, 8-chome, Nakanoshima 1-jo, Sapporo, Hokkaido, 062-8618, Japan. 8. Department of Medical Oncology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan. 9. Department of Respiratory Medicine, National Hospital Organization Asahikawa Medical Center, 7-4048 Hanasaki-cho, Asahikawa, Hokkaido, 070-8644, Japan. 10. Department of Respiratory Medicine, Tohoku University School of Medicine, 1-1 Seiryou-cho, Aoba-ku, Sendai, Miyagi, 980-8574, Japan. 11. Department of Translational Pathology, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan. 12. Department of Respiratory Medicine, KKR Sapporo Medical Center, 3-40, 6-chome, Hiragishi 1-jo, Toyohira-ku, Sapporo, Hokkaido, 062-0931, Japan.
Abstract
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.
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.
Authors: Mingjun Rui; Zijing Wang; Zhengyang Fei; Yao Wu; Yingcheng Wang; Lei Sun; Ye Shang; Hongchao Li Journal: Front Pharmacol Date: 2022-03-16 Impact factor: 5.810