Taichi Takashina1,2, Hajime Asahina3, Satoshi Oizumi1,4, Noriyuki Yamada2,4, Masao Harada4, Kei Takamura5, Hiroshi Yokouchi4,6, Toshiyuki Harada7, Osamu Honjo8, Takahiro Ogi5, Naoto Morikawa9, Ichiro Kinoshita10, Ryoichi Honda11, Kosuke Nakano4, Kenya Kanazawa6, Toraji Amano12, Hirotoshi Dosaka-Akita10, Hiroshi Isobe13, Masaharu Nishimura2. 1. Department of Respiratory Medicine, Iwamizawa Municipal General Hospital, 2 West 7, 9-jo, Iwamizawa, Hokkaido, 068-8555, Japan. 2. First Department of Medicine, Hokkaido University Hospital, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, 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 Pulmonary Medicine, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1247, Japan. 7. Center for Respiratory Diseases, JCHO Hokkaido Hospital, 3-18, 8-chome, Nakanoshima 1-jo, Sapporo, Hokkaido, 062-8618, Japan. 8. Department of Respiratory Medicine, Sapporo-Kosei General Hospital, 5 North 3, East 8, Sapporo, Hokkaido, 060-0033, Japan. 9. Division of Pulmonary Medicine, Allergy, and Rheumatology, Iwate Medical University School of Medicine, 1 Uchimaru 19, Morioka, Iwate, 020-0023, Japan. 10. 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. 11. Department of Respiratory Medicine, Sapporo Higashi Tokushukai Hospital, 3-1, Kita 33-jo Higashi 14-chome, Higashi-ku, Sapporo, Hokkaido, 065-0033, Japan. 12. Clinical Research and Medical Innovation Center, Hokkaido University Hospital, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan. 13. Department of Medical Oncology, KKR Sapporo Medical Center, 3-40, 6-chome, Hiragishi 1-jo, Toyohira-ku, Sapporo, Hokkaido, 062-0931, Japan.
Abstract
BACKGROUND: This study evaluated the efficacy and safety of switch maintenance erlotinib and bevacizumab after induction therapy with carboplatin/pemetrexed/bevacizumab for non-squamous non-small cell lung cancer (NSCLC) with wild-type EGFR. METHODS: Enrolled patients had treatment-naïve, advanced non-squamous NSCLC with wild-type EGFR. Carboplatin [area under the curve (AUC) 5.0], pemetrexed (500 mg/m2) and bevacizumab (15 mg/kg) were administered on day 1 every 3 weeks for 4-6 cycles. Maintenance therapy with erlotinib (150 mg/body) on day 1 through 21 plus bevacizumab on day 1 every 3 weeks was continued until disease progression or unacceptable toxicity. The primary endpoint was 6-month progression-free survival (PFS); secondary endpoints included overall survival (OS), overall response rate (ORR), toxicity, and quality of life (QOL). RESULTS: Fifty-one patients were enrolled between September 2011 and June 2014. The median number of cycles for induction and maintenance therapy was 4 (range 1-6) and 4 (range 1-20). Twenty-nine patients (58%) received maintenance therapy. The 6-month PFS rate was 59.5% [95% confidence interval (CI) 45.0-72.6%]. The ORR was 48.0% (95% CI 34.8-61.5%), and disease control rate was 86.0% (95% CI 73.8-93.0%). The median PFS and OS were 6.5 months (95% CI 5.8-7.2 months) and 21.4 months (95% CI 15.9-26.9 months), respectively. Although grades ≥ 3 adverse events were observed in 33 patients (66.0%), most were hematologic; there was no febrile neutropenia. QOL was maintained throughout treatment. CONCLUSIONS: Carboplatin/pemetrexed/bevacizumab followed by erlotinib and bevacizumab maintenance showed modest efficacy and was well tolerated in non-squamous NSCLC patients with wild-type EGFR. TRIAL REGISTRATION: UMIN000005872.
BACKGROUND: This study evaluated the efficacy and safety of switch maintenance erlotinib and bevacizumab after induction therapy with carboplatin/pemetrexed/bevacizumab for non-squamous non-small cell lung cancer (NSCLC) with wild-type EGFR. METHODS: Enrolled patients had treatment-naïve, advanced non-squamous NSCLC with wild-type EGFR. Carboplatin [area under the curve (AUC) 5.0], pemetrexed (500 mg/m2) and bevacizumab (15 mg/kg) were administered on day 1 every 3 weeks for 4-6 cycles. Maintenance therapy with erlotinib (150 mg/body) on day 1 through 21 plus bevacizumab on day 1 every 3 weeks was continued until disease progression or unacceptable toxicity. The primary endpoint was 6-month progression-free survival (PFS); secondary endpoints included overall survival (OS), overall response rate (ORR), toxicity, and quality of life (QOL). RESULTS: Fifty-one patients were enrolled between September 2011 and June 2014. The median number of cycles for induction and maintenance therapy was 4 (range 1-6) and 4 (range 1-20). Twenty-nine patients (58%) received maintenance therapy. The 6-month PFS rate was 59.5% [95% confidence interval (CI) 45.0-72.6%]. The ORR was 48.0% (95% CI 34.8-61.5%), and disease control rate was 86.0% (95% CI 73.8-93.0%). The median PFS and OS were 6.5 months (95% CI 5.8-7.2 months) and 21.4 months (95% CI 15.9-26.9 months), respectively. Although grades ≥ 3 adverse events were observed in 33 patients (66.0%), most were hematologic; there was no febrile neutropenia. QOL was maintained throughout treatment. CONCLUSIONS:Carboplatin/pemetrexed/bevacizumab followed by erlotinib and bevacizumab maintenance showed modest efficacy and was well tolerated in non-squamous NSCLCpatients with wild-type EGFR. TRIAL REGISTRATION: UMIN000005872.
Authors: Fabrice Barlesi; Arnaud Scherpereel; Achim Rittmeyer; Antonio Pazzola; Neus Ferrer Tur; Joo-Hang Kim; Myung-Ju Ahn; Joachim G J V Aerts; Vera Gorbunova; Anders Vikström; Elaine K Wong; Pablo Perez-Moreno; Lada Mitchell; Harry J M Groen Journal: J Clin Oncol Date: 2013-07-08 Impact factor: 44.544