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Background The selection of patients with non-small cell lung cancer (NSCLC) for immune checkpoint inhibitor (ICI) treatment remains challenging. This real-world study aimed to compare the overall survival (OS) before and after the implementation of ICIs, to identify OS prognostic factors, and to assess treatment data in first-line (1L) ICI-treated patients without epidermal growth factor receptor mutation or anaplastic lymphoma kinase translocation. Methods Data from the Danish NSCLC population initiated with 1L palliative antineoplastic treatment from 1 January 2013 to 1 October 2018, were extracted from the Danish Lung Cancer Registry (DLCR). Long-term survival and median OS pre- and post-approval of 1L ICI were compared. From electronic health records, additional clinical and treatment data were obtained for ICI-treated patients from 1 March 2017 to 1 October 2018. Results The OS was significantly improved in the DLCR post-approval cohort (n = 2055) compared to the pre-approval cohort (n = 1658). The 3-year OS rates were 18% (95% CI 15.6–20.0) and 6% (95% CI 5.1–7.4), respectively. On multivariable Cox regression, bone (HR = 1.63) and liver metastases (HR = 1.47), performance status (PS) 1 (HR = 1.86), and PS ≥ 2 (HR = 2.19) were significantly associated with poor OS in ICI-treated patients. Conclusion OS significantly improved in patients with advanced NSCLC after ICI implementation in Denmark. In ICI-treated patients, PS ≥ 1, and bone and liver metastases were associated with a worse prognosis.

Background: Optimizing clinical selection of NSCLC patients expected to benefit from immune check-point inhibition (ICI) is necessary since only a minority of patients obtain durable long-term responses. Most NSCLC patients are > 70 years old with substantial tobacco-related comorbidity and thus exposed to polypharmacy (PP). Studies exploring PPs effect on response, long-term effect, and adverse events in NSCLC patients undergoing ICI are presently lacking.Methods: Retrospective data from 118 patients with advanced or metastatic NSCLC initiating ICI (Nivolumab or Pembrolizumab) at a single-center from September 2015-April 2018 was gathered with data-cutoff at April 1st 2020. Baseline registration of PP (5 regular drugs), antibiotics and steroids (both within one month prior to ICI) and comorbidity according to Charlsons Comorbidity Score Index (CCIS) was performed. Immune-related Adverse Events (irAEs) were registered prospectively. Kaplan-Meier, logistic regression, and cox regression data analyses were performed.Results: All patients had completed ICI at time of follow-up (FU) with a median FU of 40.8 months (range 0.4-51). In multivariate survival analysis (including factors of age, CCIS, disease stage, line of treatment and performance score) median OS in the group of PP was 7.0 months compared to 24.1 months in the non-PP group (HR 2.45, p¼0.001,. Median PFS in the PP group was 2.0 versus 7.9 months (HR 2.20, P¼0.002, CI 1.35-3.60). PP correlated to radiologic response (p¼0.046). Antibiotics, prior to ICI was a negative predictor of OS and PFS. Steroid use prior but not during ICI was a negative predictor of OS. A significantly higher number of patients with PP had irAE grade 3-4 at the time of ICI termination.Conclusions: Evaluation of PP prior to ICI might aid clinical treatment decisions on ICI in NSCLC patients. Potential drug-interactions and risk of non-benefiting from ICI due to PP should be explored further in larger prospective studies on real-life NSCLC patients undergoing ICI.Legal entity responsible for the study: The authors.