| 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
(Avastin) and cetuximab (Erbitux) - 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. |