Abstract | PURPOSE: PATIENTS AND METHODS: Patients with advanced-stage non-small-cell lung cancer (NSCLC) with progression following one or two prior regimens, Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2, and measurable disease were eligible. Patients were randomly assigned to receive erlotinib (150 mg orally once a day) in combination with either placebo, R1507 9 mg/kg weekly, or R1507 16 mg/kg intravenously once every 3 weeks. Treatment cycles were repeated every 3 weeks. The primary end point was comparison of the 12-week progression-free survival (PFS) rate. RESULTS: In all, 172 patients were enrolled: median age, 61 years; female, 33%; never-smokers, 12%; and performance status 0 or 1, 88%. The median number of R1507 doses was six for the weekly arm and 3.5 for the every-3-weeks arm. Grades 3 to 4 adverse events occurred in 37%, 44%, and 48% of patients with placebo, R1507 weekly, and R1507 every 3 weeks, respectively. The 12-week PFS rates were 39%, 37%, and 44%, and the median overall survival was 8.1, 8.1, and 12.1 months for the three groups, respectively, with statistically nonsignificant hazard ratios. The 12-week PFS rate in patients with KRAS mutation was 36% with R1507 compared with 0% with placebo. CONCLUSION: The combination of R1507 with erlotinib did not provide PFS or survival advantage over erlotinib alone in an unselected group of patients with advanced NSCLC. Predictive biomarkers are essential for further development of combined inhibition of IGF-1R and EGFR.
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Authors | Suresh S Ramalingam, David R Spigel, David Chen, Martin B Steins, Jeffrey A Engelman, Claus-Peter Schneider, Silvia Novello, Wilfried E E Eberhardt, Lucio Crino, Kai Habben, Lian Liu, Pasi A Jänne, Carrie M Brownstein, Martin Reck |
Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 29
Issue 34
Pg. 4574-80
(Dec 01 2011)
ISSN: 1527-7755 [Electronic] United States |
PMID | 22025157
(Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)
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Chemical References |
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Placebos
- Quinazolines
- Erlotinib Hydrochloride
- Receptor, IGF Type 1
- teprotumumab
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Topics |
- Antibodies, Monoclonal
(administration & dosage, adverse effects)
- Antibodies, Monoclonal, Humanized
- Antineoplastic Combined Chemotherapy Protocols
(adverse effects, therapeutic use)
- Carcinoma, Non-Small-Cell Lung
(drug therapy)
- Disease-Free Survival
- Erlotinib Hydrochloride
- Female
- Humans
- Lung Neoplasms
(drug therapy)
- Male
- Middle Aged
- Placebos
(therapeutic use)
- Quinazolines
(administration & dosage, adverse effects)
- Receptor, IGF Type 1
(immunology)
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