Randomized phase II study of pemetrexed or pemetrexed plus bevacizumab for elderly patients with previously untreated non-squamous non-small cell lung cancer: Results of the Lung Oncology Group in Kyushu (LOGIK1201)

Minoru Fukuda; Takeshi Kitazaki; Daiki Ogawara; Masao Ichiki; Hiroshi Mukae; Riichiroh Maruyama; Noriaki Nakagaki; Midori Shimada; Takaya Ikeda; Junji Kishimoto; Taishi Harada; Takashi Seto; Noriyuki Ebi; Koichi Takayama; Isamu Okamoto; Yukito Ichinose; Kenji Sugio

doi:10.1016/j.lungcan.2019.01.008

Randomized phase II study of pemetrexed or pemetrexed plus bevacizumab for elderly patients with previously untreated non-squamous non-small cell lung cancer: Results of the Lung Oncology Group in Kyushu (LOGIK1201)

Lung Cancer. 2019 Jun:132:1-8. doi: 10.1016/j.lungcan.2019.01.008. Epub 2019 Apr 5.

Authors

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

Affiliations

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.

PMID: 31097081
DOI: 10.1016/j.lungcan.2019.01.008

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.

Keywords: Bevacizumab; Elderly; Lung cancer; NSqNSCLC; Pemetrexed.

Publication types

Clinical Trial, Phase II
Randomized Controlled Trial

MeSH terms

Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Bevacizumab / therapeutic use*
Carcinoma, Non-Small-Cell Lung / drug therapy*
Carcinoma, Non-Small-Cell Lung / genetics
Carcinoma, Non-Small-Cell Lung / mortality
Cost-Benefit Analysis
Female
Humans
Lung Neoplasms / drug therapy*
Lung Neoplasms / genetics
Lung Neoplasms / mortality
Male
Neoplasm Staging
Pemetrexed / therapeutic use*
Prospective Studies
Survival Analysis
Treatment Outcome

Substances

Pemetrexed
Bevacizumab