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Supplementary Tables 1-5 from Putative Predictive Biomarkers of Survival in Patients with Metastatic Pancreatic Adenocarcinoma Treated with Gemcitabine and Ganitumab, an IGF1R Inhibitor

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posted on 2023-03-31, 17:34 authored by Ian McCaffery, Yanyan Tudor, Hongjie Deng, Rui Tang, Samuel Suzuki, Sunita Badola, Hedy L. Kindler, Charles S. Fuchs, Elwyn Loh, Scott D. Patterson, Li Chen, Jennifer L. Gansert

Supplementary Table S1 (Multivariate analysis for circulating biomarkers.) Supplementary Table S2 (Summary of KRAS mutational status in the ganitumab arm.) Supplementary Table S3 (Association of KRAS mutational status with OS in the ganitumab arm.) Supplementary Table S4 (Summary of PTEN expression in the ganitumab arm.) Supplementary Table S5 (Association of PTEN expression with OS in the ganitumab arm.)

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ARTICLE ABSTRACT

Purpose: This planned exploratory analysis assessed the predictive nature of baseline circulating factors of the insulin-like growth factor (IGF) axis on the treatment effect of ganitumab (monoclonal antibody inhibitor of IGF-1 receptor) plus gemcitabine in a randomized phase II study in metastatic pancreatic adenocarcinoma.Experimental Design: Baseline levels of IGFs/IGF binding proteins (IGFBP) were analyzed in serum or plasma. Mutations and gene expression were analyzed in archival samples. Treatment effects between biomarker subgroups were compared for overall survival (OS). Associations of tumor markers with OS were evaluated.Results: For patients with evaluable samples, ganitumab was associated with improved OS versus placebo (HR, 0.49; 95% CI: 0.28–0.87). The treatment effect on improved OS was strong in the patient subset with higher levels of IGF-1, IGF-2, or IGFBP-3, or lower levels of IGFBP-2, but not so on the other corresponding subset. Median OS of ganitumab versus placebo in patients with higher levels of IGF-1, IGF-2, and IGFBP-3 was 16 versus 6.8 months (HR, 0.25; 95% CI: 0.09–0.67), 16 versus 5.9 months (HR, 0.24; 95% CI: 0.09–0.68), and 16 versus 6.8 months (HR, 0.28; 95% CI: 0.11–0.73), and in patients with lower IGFBP-2 levels was 12.7 versus 6.6 months (HR, 0.19; 95% CI: 0.07–0.55). Interaction between treatment and IGFs/IGFBPs in multivariate analyses suggested predictive potential for IGF-2 (P = 0.002) and IGFBP-2 (P = 0.02). KRAS mutation status and PTEN expression were not associated with OS.Conclusions: Baseline circulating factors of the IGF axis may predict OS benefit from ganitumab plus gemcitabine in metastatic pancreatic adenocarcinoma. Clin Cancer Res; 19(15); 4282–9. ©2013 AACR.