Phase I clinical trials in patients with advanced non-small cell lung cancer treated within a Drug Development Unit: What have we learnt?
View/ Open
Date
2017-09-01Author
Capelan, M
Roda, D
Geuna, E
Rihawi, K
Bodla, S
Kaye, SB
Bhosle, J
Banerji, U
O'Brien, M
de Bono, JS
Popat, S
Yap, TA
Type
Journal Article
Metadata
Show full item recordAbstract
OBJECTIVES: Despite advances in novel drug development for patients with advanced non-small cell lung cancer (NSCLC), there are still only a limited number of approved treatments. We therefore evaluated the clinical outcomes of patients with advanced NSCLC referred to a dedicated phase I clinical trials unit assessed baseline clinical factors associated with successful enrollment onto phase I trials. MATERIAL AND METHODS: We conducted a retrospective study involving patients with advanced NSCLC referred to the Drug Development Unit at the RMH between January 2005 and December 2013. RESULTS: 257 patients with advanced NSCLC were referred for consideration of phase I trials, of which only 89 (35%) patients successfully commenced phase I trials. The commonest reasons for not entering study included poor ECOG performance status and rapid disease progression. A multivariate analysis identified that ECOG performance status (0-1) and RMH prognostic score (0-1) were associated with successful enrollment onto phase I trials (p<0.001). Single agent therapies included novel agents against the phosphatidylinositol-3 kinase pathway, insulin growth factor-1 receptor and pan-HER family tyrosine kinases. These trial therapies were well tolerated and mainly associated with grade 1-2 adverse events, with a minority experiencing grade 3 toxicities. Nine (10%) patients, 4 with known EGFR or KRAS mutations, achieved RECIST partial responses. Median time to progression was 2.6 months and median overall survival was 8.1 months for patients enrolled. CONCLUSIONS: Phase I trial therapies were generally well tolerated with potential antitumor benefit for patients with advanced NSCLC. Early referral to drug development units at time of disease progression should be considered to enhance the odds of patient participation in these studies.
Collections
Subject
Humans
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Antineoplastic Agents
Antineoplastic Combined Chemotherapy Protocols
Neoplasm Staging
Treatment Outcome
Combined Modality Therapy
Retreatment
Odds Ratio
Aged
Aged, 80 and over
Middle Aged
Female
Male
Molecular Targeted Therapy
Neoplasm Grading
Biomarkers, Tumor
Research team
Clinical Pharmacology – Adaptive Therapy
Medicine Drug Development Unit (de Bono)
Prostate Cancer Targeted Therapy Group
Thoracic Oncology
Treatment of thoracic tumours
Medicine Drug Development Unit (Kaye)
Language
eng
Date accepted
2017-06-08
License start date
2017-09
Citation
Lung cancer (Amsterdam, Netherlands), 2017, 111 pp. 6 - 11
Publisher
ELSEVIER IRELAND LTD