Precision Medicine Clinical Trials: Successes and Disappointments, Challenges and Opportunities – Lessons Learnt

The precision medicine (PM) revolution is well underway, and next-generation sequencing (NGS) is helping take cancer treatment to new levels. Finding actionable targets in real time is now a reality, and data from several clinical trials based on identified molecular alterations can be assessed and can help address the question of whether personalized treatment based on genomics produces superior survival outcomes compared with unselected treatment. Targeted treatment-based clinical trials have shown benefit in molecular subgroups of patients. Of further interest, it appears that genomics and immunotherapy are coupled to each other, since the immune system recognizes neo-antigens produced by the mutanome. Hence, some of the most important markers predicting response to immunotherapy are genomic markers, PDL1 amplification (for PD-1/PD-L1 checkpoint inhibitors), and tumor mutational burden. However, a number of challenges remain to be addressed if the use of molecular profiling-guided therapy in PM-designed clinical trials is to become the standard on which cancer treatment is based. In this chapter, we explore what it will take for PM trials that use molecular profiling as part of the eligibility criteria to be successful and the remaining hurdles that need to be overcome.