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.

Immune checkpoint inhibitors (ICIs) are implemented as standard treatment for patients with advanced non-small cell lung cancer (NSCLC) in first-line and subsequent-line treatment. However, certain...

Convincing results from randomized controlled trials (RCTs) have led to increasing use of immune checkpoint inhibitors (ICI) as part of standard therapies in real-world (RW) scenarios. However, RW patients differ clinically from RCT populations and might have reduced long-term survival. Currently, only sparse data on 3-5-year survival rate for RW patients with advanced non-small cell lung cancer (NSCLC) treated with ICI exist. A multicenter study was performed including 729 patients with advanced NSCLC receiving monotherapy with ICI (retrospective data (n = 566) and prospective data (n = 163)). Detailed baseline clinical characteristics, programmed death-ligand 1 (PD-L1) tumor proportion score (TPS), and baseline haematological count were registered. Kaplan-Meier estimates and log-rank test were used for survival analyses, Cox regression for determination of prognostic factors. Median time of follow-up (FU) was 48.7 months (IQR 37.2-54.3). Median overall survival (OS) in first line treatment was 20.4 months (IQR 8.5-45.0) compared to 11.4 months (IQR 4.6-27.1) in ≥2nd line (HR 1.48, 95% CI 1.25-1.75). Estimated probability of OS was 30% at 3 years, 23% at 4 years, and 13% at 5 years in first line compared to 17, 13, and 11% in ≥2nd line, respectively. For those with performance status (PS) 2, the 2-year OS rate was 32% (95% CI 0.22-0.43) compared to 5% (95% CI 0.01-0.15) in patients with PD-L1 ≥ 50% versus <50%, respectively. Compared to RCTs, long-term OS and PFS rates are lower in real-world patients treated with ICI in first line but much improved compared to historic rates on chemotherapy. A promising flattening of both the OS and progression free survival curves illustrates that also a subset of real-world patients obtain long-term remission. Patients with PS 2 and PD-L1 ≥ 50% may obtain clinically meaningful 2-year PFS and OS rates.

Risk factors for systemic anticancer therapies (SACTs) administered close to death derived from existing quality indicators are not directly applicable in the clinic, because they condition on future events, which leads to selection bias. This study aimed to adapt a previously suggested indicator for its use in a clinical context and to evaluate it in a real-world, population-based cohort of cancer patients. An improved version of the '30-day mortality after SACT' indicator suggested by Wallington et al. (Lancet Oncol 2016; 17:1203-16) was defined. All SACTs (n = 16 622) for all patients (n = 10 213) treated for common malignancies between 2009 and 2019 in the North Denmark Region were included. The results for the improved and Wallington's indicators were calculated and compared. Overall, the association between clinical variables and 30-day mortality following SACT was similar for both indicators, except for the 75+ years age group. However, Wallington's indicator showed varying absolute risk when comparing values for quarterly and yearly observation intervals. The improved and Wallington's indicators showed large differences between curative (1.0% and 1.1%, respectively) and palliative SACTs (9.1% and 11.7%, respectively). For palliative SACTs, different types of malignancy presented with large variations for the improved indicator, ranging from above 10% for gastroesophageal, pancreatic and lung cancers to below 4% for prostate cancers. The value of the improved indicator was significantly lower in the last years of the study period compared with the 2009-2011 period. The type of malignancy was also associated with significant differences. We defined an indicator adapted to the clinical context evaluating 30-day mortality following SACT. This indicator can be used to identify risk factors to help with clinical decision-making. A significant downward trend was observed in the 30-day mortality following palliative SACT over an 11-year period.

Background: Not all patients with advanced non-small cell lung cancer (NSCLC) benefit from immune checkpoint inhibitors (ICIs). Therefore, we aimed to assess the predictive potential of gene expression profiling (GEP), peripheral immune cell counts, and clinical characteristics. Methods: The primary endpoint of this prospective, observational study was a durable clinical benefit (DCB) defined as progression-free survival >6 months. In a subgroup with histological biopsies of sufficient quality (n = 25), GEP was performed using the nCounter^® PanCancer IO 360 panel. Results: DCB was observed in 49% of 123 included patients. High absolute lymphocyte count (ALC) and absence of liver metastases were associated with DCB (OR = 1.95, p = 0.038 and OR = 0.36, p = 0.046, respectively). GEP showed clustering of differentially expressed genes according to DCB, and a strong association between PD-L1 assessed by GEP (CD274) and immunohistochemistry (IHC) was observed (p = 0.00013). The TGF-β, dendritic cell, and myeloid signature scores were higher for patients without DCB, whereas the JAK/STAT loss signature scores were higher for patients with DCB (unadjusted p-values < 0.05). Conclusions: ALC above 1.01 × 10⁹/L and absence of liver metastases were significantly associated with DCB in ICI-treated patients with NSCLC. GEP was only feasible in 20% of the patients. GEP-derived signatures may be associated with clinical outcomes, and PD-L1 could be assessed by GEP rather than IHC.