Challenges and Opportunities in Evaluating Novel Drug-Radiotherapy Combinations

Given the recent explosion in the number and diversity of novel targeted systemic therapies, many future advances in cancer treatment may result from improving the therapeutic ratio of radiotherapy (RT) by exploiting combinations of RT and novel targeted systemic therapies. Despite the abundance of preclinical models suggesting that new agents can improve the efficacy of RT, early-phase clinical trials have not demonstrated expected synergies or even additive efficacy between RT and these agents, particularly in trials of concurrent immunotherapy/RT. This underscores the ongoing need to develop well-formulated and well-executed early-phase clinical trials in this space that are based on sound science and are well-positioned to discern the optimal ways to combine these treatment modalities. What are the barriers to the completion of early-phase clinical trials combining RT and drugs?