Abstract LB093: Low IGFBP7 expression identifies a subset of breast cancers with favorable prognosis and sensitivity to IGF-1 receptor targeting with ganitumab: Data from I-SPY2 and SCAN-B

Abstract

Abstract Background and Hypothesis: To date, no IGF-1R targeting agent has shown clinical benefit in patients despite promising preclinical data. We hypothesized that Insulin-like growth factor binding protein-7 (IGFBP7) expression predicts response to Insulin-like growth factor-1 receptor (IGF-1R) targeting agents, for which there are no biomarkers predictive of efficacy. High IGFBP7 expression was previously associated with breast cancer progression. Materials and Methods: The predictive value of IGFBP7 expression was interrogated in I-SPY2 (NCT01042379) for pathological complete response (pCR) to neoadjuvant treatment and in SCAN-B (NCT02306096) for clinical outcome. In I-SPY2, IGFBP7 expression was examined as a predictor of pCR to neoadjuvant chemotherapy alone and separately to the combination of chemotherapy plus ganitumab (anti-IGF-1R antibody) and metformin. Odds ratios (OR) and hazard ratios (HR) with 95% confidence interval (CI) were calculated with logistic and Cox regression, respectively. Results: Higher IGFBP7 expression conferred lower odds of achieving pCR in the ganitumab/metformin plus chemotherapy arm, ORadj 0.38 (95% CI 0.17-0.80) but not in the chemotherapy-alone arm, adjusted OR 1.23 (95% CI 0.63-2.45; P interaction=0.016). In the ganitumab/metformin plus chemotherapy arm, 46.9% of patients with tumors in the lowest quartile of IGFBP7 expression achieved pCR compared to compared to only 5.6% in the highest quartile. In SCAN-B, higher IGFBP7 expression was associated with distant metastasis risk HRadj 1.41 (95% CI 1.16-1.73). Conclusion: Low IGFBP7 gene expression identifies a subset of breast cancer patients for whom the addition of ganitumab and metformin to chemotherapy results in a significantly improved pCR rate compared to neoadjuvant chemotherapy alone. Furthermore, we add to prior evidence that high IGFBP7 expression is predictive of poor outcome. Citation Format: Christopher Godina, Michael N. Pollak, Helena Jernström. Low IGFBP7 expression identifies a subset of breast cancers with favorable prognosis and sensitivity to IGF-1 receptor targeting with ganitumab: Data from I-SPY2 and SCAN-B [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB093.