This study aims to assess how clinical outcomes of immunotherapy in real-world (effectiveness) correspond to outcomes in clinical trials (efficacy) and to look into factors that might explain an efficacy-effectiveness (EE) gap. All patients diagnosed with stage IV non-small cell lung cancer (NSCLC) in 2015–2018 in six Dutch large teaching hospitals (Santeon network) were identified and followed-up from date of diagnosis until death or end of data collection. Progression-free survival (PFS) and overall survival (OS) from first-line (1L) pembrolizumab and second-line (2L) nivolumab were compared with clinical trial data by calculating hazard ratios (HRs). From 1950 diagnosed patients, 1005 (52%) started with any 1L treatment, of which 83 received pembrolizumab. Nivolumab was started as 2L treatment in 141 patients. For both settings, PFS times were comparable between real-world and trials (HR 1.08 (95% CI 0.75–1.55), and HR 0.91 (95% CI 0.74–1.14), respectively). OS was significantly shorter in real-world for 1L pembrolizumab (HR 1.55; 95% CI 1.07–2.25). Receiving subsequent lines of treatment was less frequent in real-world compared to trials. There is no EE gap for PFS from immunotherapy in patients with stage IV NSCLC. However, there is a gap in OS for 1L pembrolizumab. Fewer patients proceeding to a subsequent line of treatment in real-world could partly explain this.

Of all patients diagnosed with lung cancer, small cell lung cancer (SCLC) represents 13% of the cases in the Netherlands (Netherlands Comprehensive Cancer Organisation, 2019). SCLC is an aggressive tumour which is frequently metastasized at time of diagnosis, and therefore the majority of patients is diagnosed with extensive disease

ObjectivesMeasuring quality of care is important, however many of the quality indicators used do not focus on outcome of treatment and aspects which are valuable for patients and physicians. The project ‘Care for Outcomes’ aims to establish a relevant set of outcome indicators for lung cancer.SettingNetwork of seven large, non-university teaching hospitals in the Netherlands (Santeon).MethodsBy reviewing the literature, a list of potential outcome indicators for patients with lung cancer was composed and subsequently prioritised by expert’s opinion. Three external parties, with expertise on lung cancer, clinical management and public health, evaluated and reduced the list of indicators to a working set. Finally, the resulting selection of outcome indicators was tested for feasibility and discrimination in patient data, by collecting retrospective data and performing regression and survival analyses.ParticipantsDevelopment of the indicator set in six Santeon hospitals. Retrospective cohort study in 5922 patients diagnosed with lung cancer (all types and stages).ResultsSelected outcome indicators were divided into three levels of outcome (tiers). The first tier about survival and the process of recovery include mortality, survival, positive resection margins, rethoracotomy after resection and quality of life at baseline and after 3, 6 and 12 months. Tier 2 concerning the sustainability of the recovery include complications after resection and toxicity after chemotherapy and/or radiation. Tier 3 about sustainability of health revealed no measurable outcomes. The retrospective data collection showed differences between hospitals and variation in case mix.ConclusionA relevant set of outcome indicators for lung cancer was systematically developed. This set has the potential to compare quality of care between hospitals and inform patients with lung cancer about outcomes. The project is ongoing in the current Santeon Value-Based Health Care programme through quality and improvement cycles.

Recent discoveries in molecular diagnostics and drug treatments have improved the treatment of patients with advanced (inoperable) non-squamous non-small cell lung cancer (NSCLC) from solely platinum-based chemotherapy to more personalized treatment, including targeted therapies and immunotherapies. However, these improvements come at considerable costs, highlighting the need to assess their cost-effectiveness in order to optimize lung cancer care. Traditionally, cost-effectiveness models for the evaluation of new lung cancer treatments were based on the findings of the randomized control trials (RCTs). However, the strict RCT inclusion criteria make RCT patients not representative of patients in the real-world. Patients in RCTs have a better prognosis than patients in a real-world setting. Therefore, in this study, we developed and validated a diagnosis-treatment decision model for patients with advanced (inoperable) non-squamous NSCLC based on real-world data in the Netherlands. The model is a patient-level microsimulation model implemented as discrete event simulation with five health events. Patients are simulated from diagnosis to death, including at most three treatment lines. The base-model (non-personalized strategy) was populated using real-world data of patients treated with platinum-based chemotherapy between 2008 and 2014 in one of six Dutch teaching hospitals. To simulate personalized care, molecular tumor characteristics were incorporated in the model based on the literature. The impact of novel targeted treatments and immunotherapies was included based on published RCTs. To validate the model, we compared survival under a personalized treatment strategy with observed real-world survival. This model can be used for health-care evaluation of personalized treatment for patients with advanced (inoperable) NSCLC in the Netherlands.

Several observational studies suggested that gut microbiome-affecting-medication impairs the effectiveness of immunotherapy in patients with metastatic non-small-cell lung cancer (NSCLC). We postulated that if the effectiveness of immunotherapy is affected by drug-related changes of the microbiome, a stronger association between the use of co-medication and overall survival (OS) will be observed in patients treated with immunotherapy as compared to patients treated with chemotherapy. In a retrospective matched cohort study, immunotherapy patients were matched (1:1) to patients treated with chemotherapy in the pre immunotherapy era. The association between the use of antibiotics, opioids, proton pump inhibitors, metformin and other antidiabetics on OS was assessed with multivariable cox-regression analyses. Interaction tests were applied to investigate whether the association differs between patients treated with immuno- or chemotherapy. A total of 442 patients were studied. The use of antibiotics was associated with worse OS (adjusted Hazard Ratio (aHR) 1.39, p = 0.02) independent of the type of therapy (chemotherapy or immunotherapy). The use of opioids was also associated with worse OS (aHR 1.33, p = 0.01). The other drugs studied showed no association with OS. Interaction term testing showed no effect modification by immuno- or chemotherapy for the association of antibiotics and opioids with OS. The use of antibiotics and opioids is similarly associated with worse outcomes in both chemotherapy and immunotherapy treated NSCLC patients. This suggests that the association is likely to be a consequence of confounding rather than disturbing the composition of the microbiome.