ESMO 2025 | COSMIC-313: transcriptomic predictors of metastatic sites in RCC
Clara Steiner, MD, Dana-Farber Cancer Institute, Boston, MA & University Hospital Leipzig, Leipzig, Germany, discusses a post-hoc transcriptomic analysis from the COSMIC-313 trial (NCT03937219), which assessed cabozantinib in addition to nivolumab and ipilimumab in renal cell carcinoma (RCC). RNA sequencing of baseline tumor samples revealed distinct gene expression signatures associated with liver and lung metastases, highlighting pathways related to metabolism, hypoxia, and epithelial–mesenchymal transition. This interview took place at the European Society for Medical Oncology (ESMO) 2025 Congress in Berlin, Germany.
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Transcript
So the COSMIC-313 trial compared the combination of ipilimumab, nivolumab, and cabozantinib to nivolumab and ipilimumab alone as a large phase 3 trial. And we were fortunate to do a post-hoc analysis of a subset of 426 patients with RNA sequencing. And we did a post-hoc analysis of 426 patients that had RNA sequencing available. And we were looking for transcriptomic predictors of different sites of metastases...
So the COSMIC-313 trial compared the combination of ipilimumab, nivolumab, and cabozantinib to nivolumab and ipilimumab alone as a large phase 3 trial. And we were fortunate to do a post-hoc analysis of a subset of 426 patients with RNA sequencing. And we did a post-hoc analysis of 426 patients that had RNA sequencing available. And we were looking for transcriptomic predictors of different sites of metastases. In this analysis, we focused mostly on patients with lung metastases versus patients without lung metastases and patients with liver metastases versus patients without liver metastases. And we could see that there were some predictors that seemed to make biological sense. So for example, for the patients with lung metastases, and we could see that there were some predictors that seemed to make biological sense. So, for example, for the patients with lung metastases, we saw genes enriched from the mucin family, while for liver metastases, for example, we saw albumin, we saw transferrin, or CYP3A4. And in a sensitivity analysis, looking just at the subset of patients with nephrectomy tissue, we also saw a signal, for example, for mucin-2 for lung metastases and transferrin in the liver metastases, so that replicated in the sensitivity analysis. And we need to validate these findings in further studies, but I think it was an interesting signal.
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