NEW YORK (Reuters Health) Nov 15 - Adding the insulin-like growth factor-1 receptor (IGF-1R) monoclonal antibody R1507 to erlotinib does not improve survival in patients with advanced-stage non-small-cell lung cancer (NSCLC), a new study shows.
"Based on the strong pre-clinical data that supports the combination approach and the initial data with compounds of this class, the negative results of our study were disappointing and unanticipated," said Dr. Suresh S. Ramalingam from Emory University in Atlanta, whose findings appeared online October 24 in the Journal of Clinical Oncology.
"A similar study with figitumumab, another IGF-1R antibody (Pfizer) also yielded similar results (unpublished data)," he told Reuters Health by email.
Dr. Ramalingam and colleagues conducted a randomized phase II study of erlotinib in combination with either R1507 (weekly or every three weeks) or placebo in 171 patients with advanced-stage NSCLC. All patients had progressed following one or two prior chemotherapy regimens.
There was no significant difference between the regimens in response rate, stable disease rate or 12-week progression-free survival rate. The median progression-free survival was 1.5 months with erlotinib plus placebo, 1.87 months with erlotinib plus R1507 weekly, and 2.7 months with erlotinib plus R1507 every three weeks (all p>0.05).
Similarly, there was no significant difference in median overall survival between placebo (8.1 months) and weekly R1507 (8.1 months). With R1507 every three weeks, overall survival was slightly longer (12.1 months, p=0.04), but the hazard ratio was not significantly different from unity (p=0.09).
There were more adverse events with the R1507-erlotinib combination than with erlotinib plus placebo, and treatment discontinuation due to adverse events was more common with the experimental drug.
Patients with KRAS mutations appeared to fare better with the erlotinib-R1507 combination than with erlotinib alone, whereas the difference for patients with wild-type KRAS was not significant. Patients with EGFR mutations had better progression-free survival at 12 weeks with erlotinib alone than did patients with EGFR wild-type.
"Even the most promising compounds in development are likely to be effective in subsets of patients," Dr. Ramalingam said. "Therefore, early efforts to identify biomarkers are critical for drug development."
"R1507 is not being developed further by the sponsor," said Dr. Ramalingam said. "Our approach is to use serum IGF-1 levels for patient selection for compounds of this class."
Ramalingam has received consulting fees from Roche and other companies, and several of his co-authors are Roche employees.
SOURCE: http://bit.ly/unf9A4
J Clin Oncol 2011.
"Based on the strong pre-clinical data that supports the combination approach and the initial data with compounds of this class, the negative results of our study were disappointing and unanticipated," said Dr. Suresh S. Ramalingam from Emory University in Atlanta, whose findings appeared online October 24 in the Journal of Clinical Oncology.
"A similar study with figitumumab, another IGF-1R antibody (Pfizer) also yielded similar results (unpublished data)," he told Reuters Health by email.
Dr. Ramalingam and colleagues conducted a randomized phase II study of erlotinib in combination with either R1507 (weekly or every three weeks) or placebo in 171 patients with advanced-stage NSCLC. All patients had progressed following one or two prior chemotherapy regimens.
There was no significant difference between the regimens in response rate, stable disease rate or 12-week progression-free survival rate. The median progression-free survival was 1.5 months with erlotinib plus placebo, 1.87 months with erlotinib plus R1507 weekly, and 2.7 months with erlotinib plus R1507 every three weeks (all p>0.05).
Similarly, there was no significant difference in median overall survival between placebo (8.1 months) and weekly R1507 (8.1 months). With R1507 every three weeks, overall survival was slightly longer (12.1 months, p=0.04), but the hazard ratio was not significantly different from unity (p=0.09).
There were more adverse events with the R1507-erlotinib combination than with erlotinib plus placebo, and treatment discontinuation due to adverse events was more common with the experimental drug.
Patients with KRAS mutations appeared to fare better with the erlotinib-R1507 combination than with erlotinib alone, whereas the difference for patients with wild-type KRAS was not significant. Patients with EGFR mutations had better progression-free survival at 12 weeks with erlotinib alone than did patients with EGFR wild-type.
"Even the most promising compounds in development are likely to be effective in subsets of patients," Dr. Ramalingam said. "Therefore, early efforts to identify biomarkers are critical for drug development."
"R1507 is not being developed further by the sponsor," said Dr. Ramalingam said. "Our approach is to use serum IGF-1 levels for patient selection for compounds of this class."
Ramalingam has received consulting fees from Roche and other companies, and several of his co-authors are Roche employees.
SOURCE: http://bit.ly/unf9A4
J Clin Oncol 2011.
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