No way to clearly identify which nsclc would benefit from cetuximab

1. file:///C|/...20stories/No%20Way%20to%20Clearly%20Identify%20Which%20NSCLC%20Would%20Benefit%20From%20Cetuximab.htm[1/14/2014 2:08:32 PM]
www.medscape.com
December 06, 2013
Cetuximab combination therapy may no longer be a viable second-line treatment option for advanced non-small-cell lung cancer
(NSCLC), according to data from a phase 3 trial published online November 12 in the Lancet Oncology.
Using progression-free survival (PFS) as a primary endpoint rather than overall survival (OS) in a study of 939 unselected patients,
Edward S. Kim, MD, from the Levine Cancer Institute in Charlotte, North Caroline, and colleagues found no additional benefit when
cetuximab was added to pemetrexed.
Median PFS for the combination was 2.9 months (95% confidence interval [CI], 2.7 - 3.2 months) compared with 2.8 months (95%
CI, 2.5 - 3.3 months) for pemetrexed alone (hazard ratio, 1.03; 95% CI, 0.87 - 1.21; P = .76).
Moreover, the combination significantly increased the risk for serious adverse events (41% vs 29%, P = .0054), most notably
fatigue, acneiform rash, dyspnea, and decreased neutrophil count.
Importantly, a preplanned subanalysis by histoscore (H-score), using the standard cutoff of 200 to determine the presence of high
epidermal growth factor receptor (EGFR) expression, revealed no significant differences between groups.
"Biomarkers, including EGFR staining intensity and H-score, were not predictive in defining patients who might benefit from
cetuximab in this setting and should not be used for clinical decision making,” the authors emphasize.
The findings conflict with results from the FLEX trial, which was the first trial conducted in patients with NSCLC who were shown to
have high expression of EGRF by immunohistochemistry; the results showed a small but significant improvement in overall survival
(but not PFS) when cetuximab was added to chemotherapy (cisplantin and vinorelbine).
As previously reported by Medscape Medical News, subsequent analysis of FLEX data suggested that the benefit was limited to
patients with EGFR-overexpressing tumors, specifically those who had a high H-score.
However, this H-score did not have the same prognostic ability in subsequent retrospective studies, notes Antonio Rossi, MD, from
the Division of Medical Oncology at SG Muscati Hospital in Contrada Amoretta, Italy, in an accompanying editorial.
"Concerns about this reproducibility, and about the value of 200 as a cutoff between high versus low expression, are crucial
questions to clarify and verify prospectively before the H-score can become a validated method to select patients for cetuximab
therapy," he writes.
The title of the editorial suggests that this may be the "end of the story" for cetuximab in NSCLC.
Dr. Rossi also cited the need for more thorough preclinical studies to assess the synergy of drug combinations prior to their
approval.
"The combination of drugs without such evidence, especially for new targeted agents, should no longer be tolerated in the present
era of cancer investigation,” Dr. Rossi concluded.
The study was funded by Eli Lilly and Company and its wholly owned subsidiary, ImClone Systems LLC. Dr. Kim reports having
received research funding and honoraria from Eli Lilly. Dr. Rossi reports having served as a consultant for, and received honoraria
from, Eli Lilly.
Lancet Oncol. 2013:14:1326-1336, 1251-1253. Abstract, Editorial
Medscape Medical News © 2013 WebMD, LLC
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No Way to Clearly Identify Which NSCLC Would Benefit From Cetuximab
Yael Waknine

2. file:///C|/...20stories/No%20Way%20to%20Clearly%20Identify%20Which%20NSCLC%20Would%20Benefit%20From%20Cetuximab.htm[1/14/2014 2:08:32 PM]
Cite this article: No Way to Clearly Identify Which NSCLC Would Benefit From Cetuximab. Medscape. Dec 06, 2013.