Role of immunotherapy in stage III nonsmall cell lung cancer

Despite aggressive treatment based on definitive chemoradiotherapy, 5-year overall survival in unresectable stage III nonsmall cell lung cancer remains poor (15-20%). The novel immunotherapy based on immune checkpoint inhibitors (ICIs) presents as the therapeutic 'Holly Grail' in lung cancer treatment.

Preclinical models provide evidence of immunotherapy-radiotherapy (IM-RT) synergy. The exposure to ionizing radiation turns tumor in an in-situ vaccine, primes the innate immune system, increases immunotherapy efficacy by overcoming the immunosuppressive microenvironment of immune-resistant tumors and promotes a systemic, out-of-field antitumor T-cell-mediated response called abscopal effect. The immunomodulatory and abscopal effects of radiotherapy can be further enhanced by combining with systemic immunotherapies. The phase III START trial proved that liposomal vaccine - tecemotide (L-BLP25) administered as maintenance therapy after concurrent chemoradiotherapy (CRT) in LA-NSCLC prolongs survival. In the phase III PACIFIC trial consolidation with durvalumab, an anti-PDL-1 antibody, was associated with survival benefit in patients diagnosed with LA-NSCLC who responded to concurrent chemoradiotherapy.

PACIFIC trial results are expected to definitely establish durvalumab as standard consolidation strategy in LA-NSCLC. Many clinical trials are ongoing in the field of immunoradiotherapy in LA-NSCLC to define the optimal conditions for this therapeutic combination.