Immunotherapy: a new paradigm in the treatment of non-small cell lung cancer

Immunotherapy, in particular immune response checkpoint inhibitors, has shown to be extremely effective in terms of survival in locally advanced or metastatic nonsmall cell lung cancer, as a second line treatment in PS 0 or PS 1 patients who have progressed following platinumbased first line chemotherapy. In squamous cell cancers, nivolumab, a PD1 antibody, enables an overall survival of 9.2 months vs 6 months to be achieved, HR = 0.59; P < 0.001; in non-squamous cell carcinoma, the benefit is of the same order (12.2 months vs 9.4 months, HR = 0.73; P = 0.002), but clearly correlated to the PDL1 expression rate by the tumour cells, with no benefit for patients without expression, and a considerable benefit for those patients with strong expression. This is confirmed through trials using pembrolizumab, another PD1 antibody, with an increase in survival over docetaxel (HR = 0.71; P = 0.0008), with a more considerable benefit seen in the sub-group of patients who have PDL1 expression > 50% and, more recently, with a PDL1 antibody, atezolizumab, which in a phase II randomised study showed an increase in survival of 12.6 vs 9.7 months compared with docetaxel, HR = 0.73; P = 0.04, which correlated with the PDL1 expression rate from the tumour and immune cells. The tolerance of these drugs is good; however, with rare, but often serious immune type events, they require specific management. Numerous questions remain unanswered regarding specific populations: the elderly, those with co-morbidities, those who are PS 2 and those with brain metastases. Finally, numerous trials are ongoing, evaluating the use of these second line immunotherapies, given concomitantly or not with chemotherapy.