Over the past decade, a significant amount of clinical research has been directed at developing new and innovative therapies for advanced non-small cell lung cancer (NSCLC). Now, an analysis of clinical trials evaluating such therapies has demonstrated that the cumulative success rate for new NSCLC drugs has been lower than the industry-estimated rate. However, biomarker- and receptor-targeted therapies were found to substantially increase clinical trial success.

Findings of the study appear in the February 2014 issue of the Journal of Thoracic Oncology, the journal of the International Association for the Study of Lung Cancer (IASLC).

The analysis was designed to evaluate the risk of clinical trial failure in drug development for advanced NSCLC (stage IIIb–IV) over the past 14 years. Success was defined in relation to the likelihood that a new drug would pass all phases of clinical trial testing and be approved. Success rates were compared with rates estimated by the biopharmaceutical industry as well as rates determined by risk-analysis research in other disease indications.

During the study period, the success rate for NSCLC drug development was 11%—lower than the industry estimate of 16.5%. The analysis also showed that success rates became worse with each new phase of testing, indicating that early-phase trials may provide little help in ensuring the success of late-phase trials.

However, success rates were higher for certain drug indications. The cumulative success rate for biomarker-targeted therapy was 62%—nearly six times higher than the rate for trials without a biomarker-targeted indication (11%).


Jayson Parker, PhD, MBA

“The findings suggest that some treatment modalities and drug-design strategies may help to decrease drug-development risk and promote the development of innovative drugs to treat advanced NSCLC,” says lead author Jayson Parker, PhD, MBA, a medical biotechnology analyst in the department of biology at the University of Toronto at Mississauga.

The cumulative success rates for small-molecule and biologic drugs for advanced NSCLC were lower than industry aggregate rates: the rate for small-molecule drugs was 17% (compared with the industry aggregate of 32%), and the rate for biologic drugs was 10% (compared with 13%).

When the impact of the mechanism of action was analyzed, the cumulative success rate was 31% for receptor-targeted therapies (such as bevacizumab, crizotinib, erlotinib, and gefitinib), which was nearly threefold better than nontargeted therapies (11%). The success rate was lowest for immunotherapies (6%).


Adam Falconi, BSc

“Our analysis suggests that biomarker-targeted treatment indications and compounds that have a receptor-targeted mechanism of action offer the best chance of clinical success in this indication, and should be the focus of future clinical trial development,” says first author Adam Falconi, a community pharmacist and JD candidate at the Osgoode Hall Law School of York University, Toronto.

Clinical trials involving the use of biomarkers and receptor-targeted therapies should be a priority for patients with advanced NSCLC who wish to enroll in a clinical trial, the authors conclude.


Gilberto Lopes, MD

The third coauthor of the study, Gilberto Lopes, MD, of Johns Hopkins University School of Medicine, and HCor Onco Cancer Center for Hospital do Coração, Brazil, is a member of the IASLC career development committee.

For further information visit the International Association for the Study of Lung Cancer.