Imogen R Caldwell1, Paul Oei2, Daniel Ng2, Beth Caudwell1, Peter C C Fong1, Reuben J Broom3. 1. Adult Oncology Research Centre, Department of Medical Oncology, Auckland City Hospital, Auckland, New Zealand. 2. IGENZ Ltd, Auckland, New Zealand. 3. Adult Oncology Research Centre, Department of Medical Oncology, Auckland City Hospital, Auckland, New Zealand. Electronic address: ReubenB@adhb.govt.nz.
Abstract
BACKGROUND: The mTOR inhibitors have improved outcomes for patients with metastatic renal cell carcinoma (mRCC) but the duration of benefit is variable. Currently there are no predictive biomarkers for preselecting patients who are more likely to benefit from these agents. We undertook an exploratory translational study evaluating molecular cytogenetic changes in the context of outcomes from treatment with everolimus. PATIENTS AND METHODS: Ten patients with clear cell mRCC treated with everolimus were enrolled. Pretreatment tissue specimens were analyzed for molecular cytogenetic changes using fluorescence in situ hybridization and progression-free survival (PFS) data were obtained. Gene probes chosen for this analysis were: Von Hippel Lindau, fragile histidine triad, fibroblast growth factor receptor (FGFR) 1, FGFR3, PDGFβ, PDGFRβ, epidermal growth factor receptor, and myelocytomatosis viral oncogene. RESULTS: Median PFS was 8.75 months. Two patients with the longest PFS (28 months and 23 months) had gain of PDGFβ and PDGFRβ. This was also observed in 3 other patients who had a PFS of 11.5 months, 8 months, and 5.5 months, respectively. Cytogenetic evolution was observed between primary and metastatic specimens. CONCLUSION: PDGFβ and PDGFRβ gene status might be of relevance to everolimus therapy. Further research evaluating the utility of these potential biomarkers is required.
BACKGROUND: The mTOR inhibitors have improved outcomes for patients with metastatic renal cell carcinoma (mRCC) but the duration of benefit is variable. Currently there are no predictive biomarkers for preselecting patients who are more likely to benefit from these agents. We undertook an exploratory translational study evaluating molecular cytogenetic changes in the context of outcomes from treatment with everolimus. PATIENTS AND METHODS: Ten patients with clear cell mRCC treated with everolimus were enrolled. Pretreatment tissue specimens were analyzed for molecular cytogenetic changes using fluorescence in situ hybridization and progression-free survival (PFS) data were obtained. Gene probes chosen for this analysis were: Von Hippel Lindau, fragilehistidine triad, fibroblast growth factor receptor (FGFR) 1, FGFR3, PDGFβ, PDGFRβ, epidermal growth factor receptor, and myelocytomatosis viral oncogene. RESULTS: Median PFS was 8.75 months. Two patients with the longest PFS (28 months and 23 months) had gain of PDGFβ and PDGFRβ. This was also observed in 3 other patients who had a PFS of 11.5 months, 8 months, and 5.5 months, respectively. Cytogenetic evolution was observed between primary and metastatic specimens. CONCLUSION: PDGFβ and PDGFRβ gene status might be of relevance to everolimus therapy. Further research evaluating the utility of these potential biomarkers is required.