Kazuhiko Yamada1, Hiromi Aono2, Yukio Hosomi3, Hiroaki Okamoto4, Terufumi Kato5, Yuko Komase6, Masanori Nishikawa7, Koichi Azuma8, Hiroaki Takeoka8, Yusuke Okuma3, Yoshiro Nakahara9, Akira Sato4, Mari S Oba10, Satoshi Morita11, Hideo Kunitoh12, Koshiro Watanabe13. 1. Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan. Electronic address: kayamada@med.kurume-u.ac.jp. 2. Respiratory Medicine, Mitsui Memorial Hospital, Tokyo, Japan. 3. Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan. 4. Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen's Hospital, Kanagawa, Japan. 5. Division of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Kanagawa, Japan. 6. Department of Respiratory Internal Medicine, St. Marianna University School of Medicine, Yokohama-City Seibu Hospital, Kanagawa, Japan. 7. Department of Respiratory Medicine, Fujisawa City Hospital, Kanagawa, Japan. 8. Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan. 9. Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan; Department of Respiratory Medicine, Kitasato University School of Medicine, Kanagawa, Japan. 10. Department of Biostatistics, Yokohama City University Medical Center, Kanagawa, Japan. 11. Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan. 12. Respiratory Medicine, Mitsui Memorial Hospital, Tokyo, Japan; Department of Medical Oncology, Japanese Red Cross Medical Center, Tokyo, Japan. 13. Thoracic Oncology Research Group, Kanagawa, Japan.
Abstract
BACKGROUND: Low-dose erlotinib may be as effective as gefitinib or erlotinib at full dose in non-small cell lung cancer (NSCLC) patients with activating mutations of the epidermal growth factor receptor (EGFR) gene. METHODS: Patients with chemotherapy pretreated NSCLC harbouring EGFR mutations received erlotinib at 50 mg/d until disease progression or unacceptable toxicities. The dose was escalated to 150 mg/d in patients showing no response (i.e. without major tumour shrinkage according to Response Evaluation Criteria in Solid Tumours (RECIST)) to the initial dose during the first 4 weeks. The primary end-point was the objective response rate at the dose of 50 mg/d. RESULTS: Thirty-four patients from seven institutes were enrolled. The study was closed early when no response was confirmed in 15 patients, excluding the possibility that the primary end-point would be met. The objective response and disease control rates at the dose of 50 mg/d as determined by an independent review committee were 54.5% and 84.8%, respectively. Four additional patients achieved partial response with increased 150 mg/d dose. Progression-free survival and median survival times during the entire period of the study were 9.5 and 28.5 months, respectively. Treatment-related toxicities were generally mild, the most common being skin disorders and diarrhoea. Only one case experienced grade 3 toxicity, which was transient increase of hepatic enzymes. CONCLUSION: The primary end-point was not met; low-dose erlotinib is not recommended for fit patients with NSCLC harbouring EGFR mutations. However, it may merit further evaluation for elderly or frail patients.
BACKGROUND: Low-dose erlotinib may be as effective as gefitinib or erlotinib at full dose in non-small cell lung cancer (NSCLC) patients with activating mutations of the epidermal growth factor receptor (EGFR) gene. METHODS:Patients with chemotherapy pretreated NSCLC harbouring EGFR mutations received erlotinib at 50 mg/d until disease progression or unacceptable toxicities. The dose was escalated to 150 mg/d in patients showing no response (i.e. without major tumour shrinkage according to Response Evaluation Criteria in Solid Tumours (RECIST)) to the initial dose during the first 4 weeks. The primary end-point was the objective response rate at the dose of 50 mg/d. RESULTS: Thirty-four patients from seven institutes were enrolled. The study was closed early when no response was confirmed in 15 patients, excluding the possibility that the primary end-point would be met. The objective response and disease control rates at the dose of 50 mg/d as determined by an independent review committee were 54.5% and 84.8%, respectively. Four additional patients achieved partial response with increased 150 mg/d dose. Progression-free survival and median survival times during the entire period of the study were 9.5 and 28.5 months, respectively. Treatment-related toxicities were generally mild, the most common being skin disorders and diarrhoea. Only one case experienced grade 3 toxicity, which was transient increase of hepatic enzymes. CONCLUSION: The primary end-point was not met; low-dose erlotinib is not recommended for fit patients with NSCLC harbouring EGFR mutations. However, it may merit further evaluation for elderly or frail patients.
Authors: Ashley M Hopkins; Bradley D Menz; Michael D Wiese; Ganessan Kichenadasse; Howard Gurney; Ross A McKinnon; Andrew Rowland; Michael J Sorich Journal: Pharmacol Res Perspect Date: 2020-08