With the exciting evolution of treatment in advanced non-small cell lung cancer to incorporate either targeted therapy or immune-oncology, the future of lung cancer treatment continues to evolve. Currently we have seen the transition of immunotherapy from the palliative stage IV setting to the curative stage III setting after radical chemoradiation for unresectable stage III NSCLC. Also we have seen the impact of immunotherapy in stage IV small cell lung cancer, with approximately 15% of patients deriving major long term benefit from anti-PD-1 agents in the IMPower 133 and CASPIAN trials. The use of immunotherapy is moving towards earlier stage disease, with dramatic benefits seen with single agent (preoperative nivolumab) and combination chemo-immunotherapy as preoperative treatment in resectable NSCLC (NADIM trial). There are multiple ongoing trials exploring the impact of adjuvant and peri-adjuvant checkpoint inhibitors either as anti-PD-1 monotherapy, combination with chemotherapy or combination anti-PD-1/anti-CTLA-4 therapy in the curative setting.
In advanced disease, we must continue to develop our understanding of whether tumours are potentially sensitive to checkpoint inhibitors, and if not, why not. Is it a failure of antigen presentation or MHC machinery, a failure of T cell activation and infiltration or other challenges? With a better understanding of the immunogram of each person’s tumour, we will be able to design strategies to overcome treatment resistance, turning “cold” tumours “hot”. These may include combinations of chemotherapy and immunotherapy, combinations of checkpoint inhibitors (e.g. LAG-3 and PD-1), and targeted agents with immunotherapy, (e.g. VEGF and PD-1 inhibitors). All of these areas have growing promise with novel agents and ongoing trials. Cell therapeutics and vaccines have been more challenging to harness in lung cancer therapeutic development but ongoing studies may yet yield promise, including bespoke vaccines.
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