Minoru Fukuda1, Takeshi Kitazaki2, Daiki Ogawara3, Masao Ichiki4, Hiroshi Mukae5, Riichiroh Maruyama6, Noriaki Nakagaki7, Midori Shimada8, Takaya Ikeda9, Junji Kishimoto10, Taishi Harada11, Takashi Seto12, Noriyuki Ebi13, Koichi Takayama14, Isamu Okamoto15, Yukito Ichinose16, Kenji Sugio17. 1. Clinical Oncology Center, Nagasaki University Hospital, Nagasaki, Japan. Electronic address: mifukuda258@nifty.com. 2. Division of Respiratory Diseases, Department of Internal Medicine, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan. 3. Department of Respiratory Medicine, Sasebo City General Hospital, Nagasaki, Japan. 4. Department of Respirology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan. 5. Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. 6. Department of Thoracic Surgery, Omuta Tenryo Hospital, Omuta, Japan. 7. Department of Respiratory Medicine, Steel Memorial Yawata Hospital, Kitakyushu, Japan. 8. Division of Respiratory Diseases, Department of Internal Medicine, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan; Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. 9. Department of Respiratory Medicine, Sasebo City General Hospital, Nagasaki, Japan; Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. 10. Center for Clinical and Translational Research, Kyushu University, Fukuoka, Japan. 11. Department of Respiratory Medicine, Japan Community Health Care Organization (JCHO) Kyushu Hospital, Kitakyushu, Japan. 12. Department of Thoracic Oncology, National Kyushu Cancer Center, Fukuoka, Japan. 13. Department of Respiratory Oncology Medicine, Iizuka Hospital, Fukuoka, Japan. 14. Department of Pulmonary Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. 15. Research Institute for Disease of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 16. Clinical Research Institute, National Kyushu Cancer Center, Fukuoka, Japan. 17. Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine, Oita, Japan; Lung Oncology Group in Kyushu (LOGiK), Fukuoka, Japan.
Abstract
OBJECTIVES: To evaluate the efficacy and safety, we conducted a randomized phase II study of pemetrexed (Pem) versus Pem + bevacizumab (Bev) for elderly patients with non-squamous non-small cell lung cancer (NSqNSCLC). PATIENTS AND METHODS: The eligibility criteria were as follows: NSqNSCLC, no prior therapy, stage IIIB/IV disease or postoperative recurrence, age: ≥75 years, performance status (PS): 0-1, and adequate bone marrow function. The patients were randomly assigned (1:1 ratio) to receive Pem or Pem + Bev. The primary endpoint was progression-free survival (PFS). The secondary endpoints were the response rate, OS, toxicities, and cost-effectiveness. RESULTS:Forty-one patients were enrolled and 40 (20 from each group) were assessable. Their characteristics were as follows: male/female = 23/17; median age (range) = 78 (75-83); stage IIIB/IV/postoperative recurrence = 1/30/9; PS 0/1 = 11/29. All cases involved adenocarcinoma. There was no significant intergroup difference in PFS and the median PFS (95% confidence interval) values of the Pem and Pem + Bev groups were 5.4 (3.0-7.4) and 5.5 (3.6-9.9) months, respectively (p = 0.66). The response rate was significantly higher in the Pem + Bev group (15% vs. 55%, p = 0.0146), and there was no significant difference in OS (median: 16.0 vs. 16.4 months, p = 0.58). Grade 3 and 4 leukopenia, neutropenia, and thrombocytopenia were seen in 10 and 30, 20 and 55, and 5 and 5 cases, respectively. Drug costs were higher in the Pem + Bev group (median: 1,522,008 vs. 3,368,428 JPY, p = 0.01). No treatment-related deaths occurred. CONCLUSIONS: Adding Bev to Pem did not result in improved survival in the elderly NSqNSCLC patients. Compared with Pem + Bev, Pem monotherapy had similar effects on survival, a more favorable toxicity profile, and was more cost-effective in elderly NSqNSCLC patients. Pem monotherapy might be one of the optional regimen for NSqNSCLC patients aged ≥75 years.
RCT Entities:
OBJECTIVES: To evaluate the efficacy and safety, we conducted a randomized phase II study of pemetrexed (Pem) versus Pem + bevacizumab (Bev) for elderly patients with non-squamous non-small cell lung cancer (NSqNSCLC). PATIENTS AND METHODS: The eligibility criteria were as follows: NSqNSCLC, no prior therapy, stage IIIB/IV disease or postoperative recurrence, age: ≥75 years, performance status (PS): 0-1, and adequate bone marrow function. The patients were randomly assigned (1:1 ratio) to receive Pem or Pem + Bev. The primary endpoint was progression-free survival (PFS). The secondary endpoints were the response rate, OS, toxicities, and cost-effectiveness. RESULTS: Forty-one patients were enrolled and 40 (20 from each group) were assessable. Their characteristics were as follows: male/female = 23/17; median age (range) = 78 (75-83); stage IIIB/IV/postoperative recurrence = 1/30/9; PS 0/1 = 11/29. All cases involved adenocarcinoma. There was no significant intergroup difference in PFS and the median PFS (95% confidence interval) values of the Pem and Pem + Bev groups were 5.4 (3.0-7.4) and 5.5 (3.6-9.9) months, respectively (p = 0.66). The response rate was significantly higher in the Pem + Bev group (15% vs. 55%, p = 0.0146), and there was no significant difference in OS (median: 16.0 vs. 16.4 months, p = 0.58). Grade 3 and 4 leukopenia, neutropenia, and thrombocytopenia were seen in 10 and 30, 20 and 55, and 5 and 5 cases, respectively. Drug costs were higher in the Pem + Bev group (median: 1,522,008 vs. 3,368,428 JPY, p = 0.01). No treatment-related deaths occurred. CONCLUSIONS: Adding Bev to Pem did not result in improved survival in the elderly NSqNSCLC patients. Compared with Pem + Bev, Pem monotherapy had similar effects on survival, a more favorable toxicity profile, and was more cost-effective in elderly NSqNSCLC patients. Pem monotherapy might be one of the optional regimen for NSqNSCLC patients aged ≥75 years.