Critical evaluation of the ProfiLER-02 study design and outcomes

arising from Olivier Trédan et al. Nature Medicine https://doi.org/10.1038/s41591-025-03613-x (2025)

The ProfiLER-02 study, discussed in ref. ¹, represents a significant randomized controlled trial examining genomic testing approaches in cancer treatment. The study compared comprehensive genetic testing (324 genes) versus limited testing (87 genes) in 339 patients with advanced solid tumors to determine which approach yielded better treatment recommendations and clinical outcomes¹. The comprehensive genetic panel demonstrated superior identification of potential treatments, detecting actionable targets in 52% of patients compared to 37% with the smaller panel, a notable 15%-point increase. Additionally, more patients received molecularly-targeted treatments with comprehensive testing (14% versus 9%). However, despite identifying more treatment options, the study found no improvement in patient survival or treatment response rates, highlighting a critical gap between genomic discovery and clinical benefit¹. While this randomized controlled trial represents a valuable effort to provide patients with access to testing, several methodological limitations in its design, implementation and analysis may limit its generalizability and leave important questions for future research to address.