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Implications of key trials in advanced nonsmall cell lung cancer
Author(s) -
Bonomi Philip D.
Publication year - 2010
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.24815
Subject(s) - cetuximab , medicine , bevacizumab , kras , oncology , lung cancer , clinical trial , targeted therapy , colorectal cancer , panitumumab , epidermal growth factor receptor , randomized controlled trial , cancer , egfr inhibitors , chemotherapy
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. Cancer 2010. © 2010 American Cancer Society.