Potential Future Developments
Because tumour-targeted therapies mostly confer improvements in PFS, and immune checkpoint-targeted therapies seem to provide greater OS benefits (at least for metastatic disease), the combination of the two categories of agents may significantly improve both survival and durable responses in many cancer types. Also, the combination of immunotherapies is currently investigated in many clinical trials in multiple tumour types. By boosting the efficacy of the immune system, co-stimulatory checkpoint agonists could also be of interest to enhance the anti-tumour response generated by immune checkpoint blockers. The modulation of innate immune cells with immune checkpoint antibodies, pattern recognition receptor agonists, or oncolytic viruses could also boost the adaptive immune system. Another class of antibodies targeting both tumour cells and T cells (so-called bispecific T cell engager antibodies) is currently being evaluated and could be of interest in combination with anti-PD-L1 antibodies.
Although immune checkpoint-targeted antibodies confer long-term durable responses, a greater understanding of primary and secondary resistance mechanisms to these agents is key for the future development of cancer immunotherapy and patient selection.