Characteristics, management, and healthcare resources of patients with advanced non-small-cell lung cancer surviving 5 years after nivolumab treatment initiation: A national database analysis.

BACKGROUND: Data on long-term survivors with advanced non-small-cell lung cancer (NSCLC) treated with nivolumab are available from randomized trials. Characteristics, management, and healthcare resources of those patients need to be confirmed with real-world data. METHODS: The UNIVOC retrospective observational study included all patients with advanced NSCLC recorded in the French national hospital database starting nivolumab in 2015 and followed them until December 2020. The Kaplan-Meier method estimated the overall survival (OS). A machine learning approach identified patients with similar treatment sequences. RESULTS: Within the 3,050 patients who had nivolumab initiation,5-year OS rate was 14.6 % (95 %CI 13.3 %-16.2 %). In total, data covering at least 5 years of follow-up were retrieved for 231 surviving patients. Survivors were younger, often female and had fewer comorbidities than non-survivors. Three clusters of patients with different nivolumab treatment durations were identified: 1/ Continuous nivolumab treatment; 2/ Long period of nivolumab treatment followed by chemotherapy or no treatment; 3/ Short period of nivolumab treatment then chemotherapy or no treatment. At 5 years, 61.0 % of survivors were no longer receiving systemic therapy, 26.4 % were treated with nivolumab, 8.7 % chemotherapy, and 3.9 % other immunotherapies. Among 5-y survivor patients, the average number of hospitalisations per patient decreased from 23.4 to 12.8 between the 1st and the 5th year. In the 5th year, 46 % of patients had no more hospitalization for lung cancer. CONCLUSIONS: This large nationwide study confirms the long-term benefit of nivolumab treatment for advanced NSCLC patients in the real-world setting, with a 5-year survival rate similar to that reported in clinical trials.

Outcome following nivolumab treatment in patients with advanced non-small cell lung cancer and comorbid interstitial lung disease in a real-world setting.

Background: Up to 10% of patients with advanced non-small cell lung cancer (aNSCLC) have pre-existing interstitial lung disease (ILD). These patients are usually excluded from immunotherapy clinical trials. Consequently, knowledge on outcomes following nivolumab treatment in these patients remains limited. The primary objective of this study was to evaluate survival outcome following nivolumab treatment in ILD patients with pre-treated aNSCLC in the real-world setting. Patients and methods: The study included all patients with aNSCLC recorded in the French hospital database, starting nivolumab in 2015-2016. Patients were stratified by pre-existing ILD and three subgroups were studied [auto-immune or granulomatous (AI/G) ILD, other known causes ILD and idiopathic ILD]. Time to discontinuation of nivolumab treatment [time to treatment duration (TTD)] and overall survival (OS) were estimated using Kaplan-Meier survival analysis. Results: Of 10,452 aNSCLC patients initiating nivolumab, 148 (1.4%) had pre-existing ILD. Mean age at nivolumab initiation was 64.6 ± 9.4 years in ILD and 63.8 ± 9.6 years in non-ILD. Compared to non-ILD, patients in the ILD group were more frequently men (p < 0.05) and had more comorbidities (p < 0.001). There was no significant difference between ILD and non-ILD groups for median TTD (2.5 versus 2.8 months; p = 0.6) or median OS (9.6 versus 11.9 months; p = 0.1). Median OS in AI/G ILD (n = 14), other known causes ILD (n = 75), and idiopathic ILD (n = 59) were 8.6, 10.7, and 9.6 months, respectively. Conclusion: In this large cohort of aNSCLC patients with ILD, outcomes are similar to those obtained in the non-ILD population. Immunotherapy could be beneficial for these patients.

Long-term hospital resource utilization and associated costs of care for patients initiating nivolumab in advanced non-small cell lung cancer in France.

OBJECTIVES: In advanced cancers, healthcare resource utilization (HCRU) and costs usually increase until death. However, few studies have measured HCRU over time in patients treated with immunotherapies. The objective was to describe the evolution of HCRU and costs over four years for patients with advanced non-small cell lung cancer (aNSCLC) initiating nivolumab. MATERIALS AND METHODS: Based on the French hospital reimbursement database, all aNSCLC patients initiating nivolumab in the 2nd line or later in 2015 or 2016 were followed until 2019. HCRU (including hospitalizations and hospital visits) and costs (payer perspective) were described annually after nivolumab initiation. Trends in HCRU were analyzed with the Mann-Kendall test. As most patients did not reach the four-year follow-up, cost-analysis was performed without adjustment throughout, without adjustment in uncensored cases only or with adjustment using for all patients using the Bang&Tsiatis method. RESULTS: 10,452 patients initiating nivolumab were evaluated. The percentage of patients hospitalized or with hospital visits decreased (p < .001) over the four-year follow-up with the exception of consultations. The number of hospital visits per patient decreased from 23.3 in Y1 to 13.2 in Y4 without adjustment and 18.3 with adjustment (p < .001). The overall hospitalization duration per patient (days) decreased from 36.0 (Y1) to 14.9 (Y4-unadjusted) and 20.5 (Y4-adjusted) (p < .001). Annual per capita costs also decreased. The method without adjustment provided the lowest cost over time (€44,404 (Y1), €32,206 (Y2); €28,552 (Y3); €18,841(Y4)) while the Bang&Tsiatis method presented the highest cost (€45,002 (Y1), €36,330 (Y2); €35,080 (Y3); €28,931 (Y4)). CONCLUSION: HCRU and costs for NSCLC patients treated with nivolumab decreased over time. Cost estimates are dependent on the statistical method used to take into account uncertainty, but costs decreased over time whatever the method used.

Automatic and Explainable Labeling of Medical Event Logs With Autoencoding.

Process mining is a suitable method for knowledge extraction from patient pathways. Structured in event logs, medical events are complex, often described using various medical codes. An efficient labeling of these events before applying process mining analysis is challenging. This paper presents an innovative methodology to handle the complexity of events in medical event logs. Based on autoencoding, accurate labels are created by clustering similar events in latent space. Moreover, the explanation of created labels is provided by the decoding of its corresponding events. Tested on synthetic events, the method is able to find hidden clusters on sparse binary data, as well as accurately explain created labels. A case study on real healthcare data is performed. Results confirm the suitability of the method to extract knowledge from complex event logs representing patient pathways.

Immunotherapy rechallenge after nivolumab treatment in advanced non-small cell lung cancer in the real-world setting: A national data base analysis.

OBJECTIVES: Nivolumab is now a reference treatment for patients with advanced non-small cell lung cancer (NSCLC) after failure of prior platinum-based chemotherapy. Little data are available on treatment approaches following discontinuation of nivolumab and on the interest of a second course of immunotherapy after nivolumab discontinuation. The aims of this study were to describe treatment pathways following nivolumab discontinuation and to describe survival following retreatment with immunotherapy. MATERIALS AND METHODS: The analysis includes all patients with NSCLC recorded in a national hospital database, starting nivolumab in 2015-2016. Nivolumab treatment was considered discontinued if ≥3 infusions were missed. Patients starting a second course of PD-1 inhibitor following nivolumab discontinuation were analysed according to the duration of their initial nivolumab treatment course. RESULTS: 10,452 patients were included (71 % men; mean age: 63.8 ± 9.6 years; squamous histology: 44 %). Median nivolumab treatment duration was 2.8 months [IQR :1.4-6.9]. Median OS was 11.5 months [95 %CI: 11.1-11.9]; 5118 (53.4 %) patients received post nivolumab therapy lines: 1517 (29.6 %) of these received a second course of PD-1 inhibitor, either after a treatment-free interval (resumption: n = 1127) or after intervening chemotherapy (rechallenge: n = 390). Median OS after nivolumab discontinuation was 15.0 months [13.9-16.7] in the resumption group and 18.4 months [14.8-21.9] in the rechallenge group. Median OS was significantly longer in patients with an initial nivolumab treatment duration ≥3 months. CONCLUSION: In this real-world setting, outcome after retreatment with a PD-1 inhibitor following a first course of nivolumab was significantly better in patients with a longer duration of initial nivolumab treatment.

Nivolumab treatment in advanced non-small cell lung cancer: real-world long-term outcomes within overall and special populations (the UNIVOC study).

OBJECTIVE: To describe long-term outcomes of patients treated with nivolumab for advanced non-small cell lung cancer (aNSCLC) in everyday clinical practice in France, with a focus on patients aged ⩾80 years, patients with renal impairment and patients with brain metastases. METHODS: The study included all patients with aNSCLC recorded in the French national hospital database, starting nivolumab in 2015-2016 and followed until December 2018. Patients were stratified by age, the presence of renal impairment and brain metastasis, as documented in the hospital discharge summaries. Information was retrieved on demographics, comorbidities and treatment history at baseline. Time to discontinuation of nivolumab treatment and overall survival were estimated using Kaplan-Meier survival analysis. RESULTS: Overall, 10,452 patients were included, of whom 514 were octogenarians, 479 had renal impairment and 1800 had brain metastases at baseline. Median duration of nivolumab treatment was 2.8 months in the overall population and in both the octogenarian and renally impaired subgroups, and 2.3 months in patients with brain metastases. Median overall survival in these patient groups was 11.7 months (95% confidence interval: 11.3-12.2), 11.7 months (11.3-12.1), 11.7 months (11.3-12.2) and 9.9 months (9.0-10.9) respectively. Three-year overall survival rates were 19.1% (18.1-20.2) in the overall population, 16.5% (11.6-23.4) in octogenarians, 15.9% (11.8-21.4) in patients with renal impairment and 21.7% (19.4-24.2) in those with brain metastases. CONCLUSION: This large nationwide retrospective real-life cohort provided narrow estimates of long-term overall survival, which reached 19% at 3 years, consistent with data from phase III trials of nivolumab. Survival rates were comparable in the three special populations of interest and the overall population.

Hospital costs impact of post ischemic stroke dysphagia: Database analyses of hospital discharges in France and Switzerland.

INTRODUCTION: Oropharyngeal dysphagia is frequent in hospitalized post-stroke patients and is associated with increased mortality and comorbidities. The aim of our analysis was to evaluate the impact of dysphagia on Length of Hospital Stay (LOS) and costs. The hospital perspective was used to assess costs. METHODS: Hospital discharge databases comparing hospital stays for ischemic stroke associated with dysphagia vs stroke without dysphagia in France and Switzerland were analyzed. The French Medical Information System Program (PMSI) database analysis focused on 62'297 stays for stroke in the public sector. 6'037 hospital stays for stroke were analyzed from the Swiss OFS (Office fédéral de la statistique: Statistique des coûts par cas 2012) database. Diagnosis codes and listing of procedures were used to identify dysphagia in stroke patients. RESULTS: Patients with post-stroke dysphagia accounted for 8.4% of stroke hospital stays in Switzerland, which is consistent with recently reported prevalence of dysphagia at hospital discharge (Arnold et al, 2016). The French database analysis identified 4.2% stays with post-stroke dysphagia. We hypothesize that the difference between the Swiss and French datasets may be explained by the limitations of an analysis based on diagnosis and procedure coding. Patients with post-stroke dysphagia stayed longer at hospitals (LOS of 23.7 vs. 11.8 days in France and LOS of 14.9 vs. 8.9 days in Switzerland) compared with patients without post-stroke dysphagia. Post-stroke dysphagia was associated with about €3'000 and CHF14'000 cost increase in France and Switzerland respectively. DISCUSSION: In this study post-stroke dysphagia was associated with increased LOS and higher hospital costs. It is difficult to isolate the impact of dysphagia in patients with multiple symptoms and disabilities impacting rehabilitation and recovery. After adjusting for confounding factors by matching stays according to age, sex and stroke complications, post-stroke dysphagia association with increased LOS and higher hospital costs was found to be independent of sensory or motor complications. CONCLUSION: Post-stroke dysphagia is associated with increased length of hospital stay and higher hospital costs.

How did chronic hepatitis C impact costs related to hospital health care in France in 2009?

AIMS: To evaluate the health care burden of chronic hepatitis C (CHC) in French hospitals. METHODS: All hospital stays with CHC ICD-10 code were extracted from the 2009 French hospital discharge database and classified in five groups: non-complicated CHC, liver cirrhosis (CIR), hepatocarcinoma (HCC), liver transplantation (LT) and unclassified. Hospital costs were calculated according to the French official prices and expressed in 2010 euro. The economic analysis was carried out from the Social Security point of view. RESULTS: Twenty-seven thousand two hundred and fifty-eight of the 68,683 hospital stays with CHC ICD-10 code corresponding to 15,482 patients were considered as directly related to HCV: 52% for non-complicated CHC, 33% for CIR, 11% for HCC, 2% for LT and 2% unclassified. The total cost of hospital stays for CHC and its complications was estimated at 65,956,938 €. Almost half (47%) of total costs were attributable to CIR while HCC and LT contributed to 18% and 19%, respectively. CONCLUSION: This first analysis of the French hospital discharge database focused on CHC brings new and essential information. It shows that 84% of HCV-related hospital costs are attributable to advanced liver diseases. Together with more efficient therapies, enhancing screening and access to treatment policies could substantially relieve the hospital burden of CHC.

Economic burden of osteoporosis in women: data from the 2008 French hospital database (PMSI).

OBJECTIVES: To estimate the number and costs of hospitalisations associated with osteoporosis in France. METHODS: Data for women aged 50 years and over were extracted from the 2008 French Hospital National Database. Criteria for acute care were established according to ICD-10 codes related to osteoporosis. As coding rules are not systematically used, an additional extraction which included surgical stays for hip fractures was performed in order to be more exhaustive. The two datasets were merged and duplicate stays excluded. Among women hospitalised in acute care during 2008, we selected those progressing to rehabilitation care within the year. We assessed the numbers of hospitalisations and women, proportion of surgical management, length of stay in acute care and numbers of rehabilitation days and costs. Hospital costs were calculated according to the National Hospital Tariff and National Scale of Costs, respectively, for acute and rehabilitation care based on 2009 tariffs. RESULTS: There were 67.807 hospitalisations (64.793 patients) associated with osteoporosis; 83% of total hospitalisations were in patients aged ≥75 years. A total of 80% of hospitalisations were associated with surgical management of fractures and 31.458 patients (49%) progressed from hospitalisation to rehabilitation. The mean ±SD length of stay was 12±8 days for hospitalisation and 43±31 days for rehabilitation care. The overall cost of hospitalisations was €415.4 million, of which 4.2% was related to medical devices. The overall cost of rehabilitation was €331.8 million. CONCLUSIONS: In 2008, postmenopausal osteoporosis was associated with a substantial economic burden at hospital in France.