Immune-related adverse events and nivolumab outcomes in non-small cell lung cancer patients: A multi-institutional, retrospective cohort study

Background: Immune checkpoint inhibitors are routinely used in Non Small Cell Lung Cancer (NSCLC) patients following progression on first-line therapy. Immune-related Adverse Events (IrAEs) have been associated with the efficacy of PD-1 inhibitors in melanoma. The association between the development of IrAEs and efficacy of nivolumab remains unclear in NSCLC. Methods: We retrospectively collected data from patients who received nivolumab for advanced NSCLC on an Open Access Program across seven oncology institutions in Queensland, Australia, and analyzed whether there was an association between outcomes and the development of immune-related toxicity. Results: One hundred and ninety six patients were enrolled to this ethics committee approved audit – 77 females (39%) and 119 (61%) males; PS 0-1 (62%); PS 2-3 (38%); median age 67 (range 42-84). An objective response was recorded in 24% of patients; partial response (47/196) with one complete response, in addition 28% (55/196) had stable disease. The median overall survival was 9.2 months; 13.4 months in PS 0-1 patients and 4.2 months in PS 2-3 patients. At 1 year, the overall survival rate was 42%; 57% in patients with PS 0-1 and 18% in PS 2-3 patients. The presence of IrAEs of any grade occurred in 36% of patients and was associated with a longer median PFS of 5.9 months versus 2.3 months (P value < 0.01, 95% CI) in patients with no immune toxicity on Kaplan Meier analysis. The median OS of patients experiencing an IrAE was 24.3 months compared with 6.5 months without (P value < 0.01, 95% CI). A durable clinical benefit was observed in 72% of patients who developed at least one IrAE versus 37% in those without any immune mediated toxicity. Analysis of the prognostic relevance of routine histological, hematological and biochemical parameters is ongoing with a multivariate analysis planned. Conclusions: Nivolumab had clinically significant long-term benefits in the treatment of locally advanced and metastatic NSCLC wit