Related Experiment Video
Updated: Jun 16, 2026
Ultra-Fast Amplicon-Based Next-Generation Sequencing in Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Implications of key trials in advanced nonsmall cell lung cancer
1Division of Hematology/Oncology, Rush University Medical Center, Chicago, IL, USA. philip_bonomi@rsh.net
Abstract:
Many different targeted therapies with varying mechanisms of action have been added to standard first-line chemotherapy doublets in an effort to improve survival of patients with advanced nonsmall cell lung cancer (NSCLC). Only 2 targeted therapies-bevacizumab and cetuximab-have been associated with superior survival in phase 3 first-line studies. For both agents, the decision to enter phase 3 was based on results from randomized phase 2 trials, unlike other targeted therapies where the decision was made using either phase 1 or single study arm phase 2 results. There is also mounting evidence that patient selection will play a key role in the successful development of any targeted agent. Bevacizumab is indicated for patients with nonsquamous NSCLC who do not have certain comorbidities. Use of cetuximab is not restricted by safety factors, but may be focused on patients whose tumors are epidermal growth factor receptor (EGFR)-dependent; whether EGFR expression or absence of KRAS mutations are appropriate markers is still under study. By including randomized phase 2 trials in the development pathway, and by improving patient selection for individual agents (enriching trials with patients most likely to respond), it may be possible to enhance the success rate of future phase 3 clinical trials and, in turn, define future clinical practice with improved patient outcomes.
Insights
Targeted therapies improve advanced non-small cell lung cancer (NSCLC) survival when selected using randomized phase 2 trials and patient stratification. This approach enhances the success of phase 3 trials and future clinical practice for NSCLC patients.
Area of Science:
- Oncology
- Clinical Trials
- Targeted Therapy
Background:
- Advanced non-small cell lung cancer (NSCLC) treatment often involves adding targeted therapies to standard chemotherapy.
- Bevacizumab and cetuximab are the only targeted therapies demonstrating improved survival in first-line phase 3 NSCLC studies.
- Previous targeted therapies advanced to phase 3 based on phase 1 or single-arm phase 2 data.
Purpose of the Study:
- To evaluate the role of randomized phase 2 trials and patient selection in the development of targeted therapies for advanced NSCLC.
- To identify strategies for improving the success rate of phase 3 clinical trials for targeted agents in NSCLC.
Main Methods:
- Review of targeted therapy development pathways for advanced NSCLC.
- Analysis of factors contributing to the success of bevacizumab and cetuximab in phase 3 trials.
- Discussion of patient selection strategies, including comorbidity assessment for bevacizumab and potential biomarkers (EGFR dependence, KRAS mutations) for cetuximab.
Main Results:
- Bevacizumab and cetuximab's success in phase 3 trials was preceded by randomized phase 2 data.
- Patient selection is crucial for targeted therapy efficacy, with specific criteria for bevacizumab and ongoing research for cetuximab biomarkers.
- Incorporating randomized phase 2 trials and improved patient selection may increase the likelihood of successful phase 3 trials.
Conclusions:
- Randomized phase 2 trials are a valuable step in the development of targeted therapies for advanced NSCLC.
- Enhanced patient selection strategies can improve the efficacy and success rates of targeted agents in NSCLC clinical trials.
- Optimizing the development pathway for targeted therapies holds promise for improved patient outcomes in advanced NSCLC.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against specific...
02:56Treatment Resistent Cancers
01:11Clinical Trials: Overview