Ganitumab and Metformin plus Standard Neoadjuvant Therapy in Stage 2/3 Breast Cancer: Results from the I-SPY2 Adaptively Randomized Platform Trial

Ganitumab and Metformin was one of the experimental regiments evaluated in I-SPY 2, a neoadjuvant platform trial for high risk, early stage breast cancer. Based on the hypotheses that pre-treatment IGF-1R axis signaling at the expression level may predict response to Ganitumab and Metformin, in pre-defined analyses we assessed 11 genes involved in IGF1R pathway signaling, the IGFBP5/IGFBP4 ratio, and two IGFR expression signatures to test their association with pCR (complete pathologic response). Fresh-frozen pre-treatment breast cancer tumors (n=233: 106 Ganitumab arm, 127 control arm) from the neoadjuvant ISPY2 trial for high risk, early-stage breast cancer were assayed using GPL16233 (n=70) or GPL20078 (n=163) expression arrays; and these data were combined into a single gene-level dataset after batch-adjusting using ComBat. The sample characteristics and their values represent: HER2: the status of the HER2 gene. 1 = positive; 0 = negative. HR: the status of hormone (estrogen and progesterone) receptors 1 = positive; 0 = negative. pCR: the status of a pathological complete response (pCR) 1 = complete response; 0 = failed complete response MP: MammaPrint status 0 = MammaPrint high 1 (MP1); 1 = MammaPrint (ultra) high 2 (MP2) Arm: arm of the trial per patient - 'Ganitumab arm' or 'Control arm'. Originally, a ComBat batch correction process was applied to the raw data on a larger group of patients (~900), which we cannot release. Linear adjustment factors from this group were derived so they can be applied to this smaller group of 233 patients. The ISPY2_LinearFit_forCombiningExp files contain linear adjustments to go from raw to batch corrected data. For fully normalized and batch corrected data on the gene level, please use ISPY2ResID_AgilentGeneExp_GanitumabPlusCtr_FrshFrzn_meanCol_geneLevel_n233.txt, provided in the supplementary files. For biomarkers, including 11 genes involved in IGF1R pathway signaling, the IGFBP5/IGFBP4 ratio, and two IGFR expression signatures (as used in the publication), please use ISPY2ResID_Ganitumab_biomarkers_20210607.csv, provided in the supplementary files.