Despite current therapeutic options metastatic non- small-cell lung
cancer (NSCLC) remains incurable. Targeted therapies have opened new
opportunities for several molecular subtypes, but virtually all patients
treated will ultimately develop progressive disease by treatment
resistance. Recent clinical trials have shown that immune-checkpoint
blockade can result in striking and durable responses in metastatic
NSCLC. These impressive results are yet to be confirmed in following
trials; nonetheless, NSCLC therapeutic strategies will most likely need
to integrate immune-checkpoint inhibitors in the near future.
Interestingly, conventional therapies are capable of modulating the
immune system and can therefore interact directly or indirectly with
immunotherapies. This suggests that some combinations might have
synergistic activity and lead to improved efficacy. Conventional and
targeted therapies can induce rapid tumor lysis, and immune-checkpoint
blockade can then help to induce a sustained immune-mediated tumor
control. Moreover, the distinctive toxicity profile associated with
immune-checkpoint modulators makes them good candidates for combination
strategies. Here we summarize the results of immune-checkpoints trials
in NSCLC, and also report how current therapeutic options can modulate
the immune system. We provide a rationale and identify potential
challenges for immune-checkpoint blockade combinations with conventional
therapeutics in NSCLC