To estimate the average treatment effect of immune checkpoint inhibitors in any line of treatment in a 2016-2018 population-based cohort of patients with advanced non-small-cell lung cancer (NSCLC).

The cohort, and information on the tumor, were derived from the cancer registry of the Agency for Health Protection of Milan, Italy. Inclusion criteria were adult age, microscopically confirmed NSCLC, stage IIIB or IV at diagnosis, and having received at least one line of treatment. Treatment with all licensed anti PD-1/PD-L1 inhibitors was derived from inpatients and outpatients' pharmaceutical databases of the ATS and vital status at 31 December 2019 from the health registry office of the Lombardy region. We investigated, with a causal approach, the relationship between survival and anti PD-1/PD-L1 treatment at any line constructing a directed acyclic graph and fitting a Marginal Structural Cox Model (MSCM).

Of 1673 subjects, 324 received anti PD-1/PD-L1 at any treatment line. Overall, one-year survival was 61.1% (95 %CI, 55.6-66.2%) in the group treated with anti PD-1/PD-L1 at any line and 31.1% (95 %CI, 28.6-33.5%) among not treated. One-year hazard ratio (HR) of death for not treated vs. treated was 2.15 (95 %CI, 1.91-2.41), decreasing to 1.23 (95 %CI, 1.03-1.46) at two years and reaching one in the third year.

In un unselected population-based cohort with advanced lung cancer, treatment with anti PD-1/PD-L1 at any line lowered the hazard of death up to two-years from date of diagnosis, confirming the efficacy of immunotherapy outside clinical trials.