Population characteristics, management, and survival outcomes in muscle-invasive urothelial carcinoma undergoing radical resection: the MINOTAUR study.

PURPOSE: To describe the incidence, management, and survival outcomes of patients with muscle-invasive urothelial carcinoma (MIUC) undergoing radical surgery (RS) in France. METHODS: We relied on a non-interventional real-world retrospective study based on French National Hospitalization Database. Adults with MIUC with a first RS between 2015 and 2020 were selected. Subpopulations of patients with RS performed in 2015 and 2019 (pre-COVID-19) were extracted, according to cancer site: muscle-invasive bladder cancer (MIBC) or upper tract urothelial carcinoma (UTUC). Disease-free and overall survival (DFS, OS - Kaplan-Meier) were assessed on the 2015 subpopulation. RESULTS: Between 2015 and 2020, 21,295 MIUC patients underwent a first RS. Of them, 68.9% had MIBC, 28.9% UTUC, and 2.2% both cancers. Apart from fewer men among UTUC (70.2%) than MIBC patients (90.1%), patients' demographic (mean age ~ 73 years) and clinical characteristics were similar whatever the cancer site or year of first RS. In 2019, RS alone was the most frequent treatment, occurring in 72.3% and 92.6% in MIBC and UTUC, respectively. Between 2015 and 2019, neoadjuvant use rate increased from 13.8% to 22.2% in MIBC, and adjuvant use rate increased from 3.7% to 6.3% in UTUC. Finally, median [95% confidence interval] DFS times were 16.0 [14.0-18.0] and 27.0 [23.0-32.0] months among MIBC and UTUC, respectively. CONCLUSION: Among patients with resected MIUC annually, RS alone remained the main treatment. Neoadjuvant and adjuvant use increased between 2015 and 2019. Nonetheless, MIUC remains of poor prognosis, highlighting an unmet medical need, notably among patients at high risk of recurrence.

A Review of Overall Survival Extrapolations of Immune-Checkpoint Inhibitors Used in Health Technology Assessments by the French Health Authorities.

OBJECTIVES: Extrapolation is often required to inform cost-effectiveness (CE) evaluations of immune-checkpoint inhibitors (ICIs) since survival data from pivotal clinical trials are seldom complete. The objectives of this study were to evaluate the accuracy of estimates of long-term overall survival (OS) predicted in French CE assessment reports of ICIs, and to identify models presenting the best fit to the observed long-term survival data. METHODS: A systematic review of French assessment reports of ICIs in the metastatic setting since inception until May 2020 was performed. A targeted literature review was conducted to collect associated extended follow-up of randomized controlled trials (RCTs) used in the CE assessment reports. Difference between projected and observed OS was calculated. A range of standard parametric and spline-based models were applied to the extended follow-up data from the RCT to determine the best-fitting survival models. RESULTS: Of the 121 CE assessment reports published, 11 reports met the inclusion criteria. OS was underestimated in 73 percent of the CE assessment reports. The mean relative difference between each source was -13 percent (median: -15 percent; IQR: -0.4 to 26 percent). Models providing the best fit were those that could reflect nonmonotonic hazards. CONCLUSIONS: Based on the available data at the time of submission, longer-term survival of ICIs was not fully captured by the extrapolation models used in CE assessments. Standard and flexible parametric models which can capture nonmonotonic hazard functions provided the best fit to the extended follow-up data. However, these models may still have performed poorly if fitted to survival data available at the time of submission to the French National Authority for Health.

Integrating Quality of Life in the Care Pathway of Cancer Patients Undergoing Immunotherapy Treatment: Descriptive, Cross-sectional Survey of an Online Patient Community's Experiences and Expectations.

BACKGROUND: New cancer treatments, such as immune checkpoint inhibitors (ICIs), can improve survival and health-related quality of life (HRQoL) in patients with cancer. Although long-term monitoring of HRQoL has been shown to improve survival, integration of HRQoL into everyday practice remains poorly documented. OBJECTIVE: This study describes experiences and expectations of patients treated with ICIs regarding a discussion of HRQoL with health care professionals (HCPs) in cancer management. METHODS: This cross-sectional study was conducted in an online patient community (Carenity) in France. Patients treated with ICIs for cancer, included between September 2018 and January 2019, completed a questionnaire to assess the involvement of HCP in a discussion of HRQoL and when and what was discussed. RESULTS: Of 82 patients included (mean age: 56.9 years, 95% CI 54.2-59.6; 46 [56%] male; 34 [41%] with lung cancer), 62 (76%) reported discussing HRQoL at least once with HCPs, mainly general practitioners (54/82, 66%), oncologists (53/82, 65%), and hospital nurses (50/82, 61%). Around half (45/82, 55%) of the patients were satisfied with these discussions. Discussions with the oncologist were at the patient's initiative (34/53, 64%). Discussions occurred primarily during follow-up visits (40/62, 65%), when adverse events occurred (30/62, 48%), and at treatment initiation (27/62, 32%). The most discussed dimensions were symptoms (48/62, 77%) and physical well-being (43/62, 69%). With respect to expectations, 54/82 (66%) patients considered oncologists as the most important HCPs for discussing HRQoL. These discussions were desirable throughout the care pathway, particularly at diagnosis (63/82, 77%) and when treatment was initiated (75/82, 92%) or changed (68/82, 83%). All HRQoL dimensions were considered important to discuss. CONCLUSIONS: With only around half of the patients satisfied with HRQoL discussions, impactful HRQoL integration in clinical practice is critical. According to patients, this integration should involve mainly oncologists and general practitioners, should happen at every step of the care pathway, and should be extended to dimensions that are currently rarely addressed.

Exploring the Health-Related Quality of Life of Patients Treated With Immune Checkpoint Inhibitors: Social Media Study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are increasingly used to treat several types of tumors. Impact of this emerging therapy on patients' health-related quality of life (HRQoL) is usually collected in clinical trials through standard questionnaires. However, this might not fully reflect HRQoL of patients under real-world conditions. In parallel, users' narratives from social media represent a potential new source of research concerning HRQoL. OBJECTIVE: The aim of this study is to assess and compare coverage of ICI-treated patients' HRQoL domains and subdomains in standard questionnaires from clinical trials and in real-world setting from social media posts. METHODS: A retrospective study was carried out by collecting social media posts in French language written by internet users mentioning their experiences with ICIs between January 2011 and August 2018. Automatic and manual extractions were implemented to create a corpus where domains and subdomains of HRQoL were classified. These annotations were compared with domains covered by 2 standard HRQoL questionnaires, the EORTC QLQ-C30 and the FACT-G. RESULTS: We identified 150 users who described their own experience with ICI (89/150, 59.3%) or that of their relative (61/150, 40.7%), with 137 users (91.3%) reporting at least one HRQoL domain in their social media posts. A total of 8 domains and 42 subdomains of HRQoL were identified: Global health (1 subdomain; 115 patients), Symptoms (13; 76), Emotional state (10; 49), Role (7; 22), Physical activity (4; 13), Professional situation (3; 9), Cognitive state (2; 2), and Social state (2; 2). The QLQ-C30 showed a wider global coverage of social media HRQoL subdomains than the FACT-G, 45% (19/42) and 29% (12/42), respectively. For both QLQ-C30 and FACT-G questionnaires, coverage rates were particularly suboptimal for Symptoms (68/123, 55.3% and 72/123, 58.5%, respectively), Emotional state (7/49, 14% and 24/49, 49%, respectively), and Role (17/22, 77% and 15/22, 68%, respectively). CONCLUSIONS: Many patients with cancer are using social media to share their experiences with immunotherapy. Collecting and analyzing their spontaneous narratives are helpful to capture and understand their HRQoL in real-world setting. New measures of HRQoL are needed to provide more in-depth evaluation of Symptoms, Emotional state, and Role among patients with cancer treated with immunotherapy.

Access to innovative drugs for metastatic lung cancer treatment in a French nationwide cohort: the TERRITOIRE study.

BACKGROUND: Territorial differences in the access to innovative anticancer drugs have been reported from many countries. The objectives of this study were to evaluate access to innovative treatments for metastatic lung cancer in France, and to assess whether socioeconomic indicators were predictors of access at the level of the municipality of residence. METHODS: All incident cases of metastatic lung cancer hospitalised for a chemotherapy in public hospitals in 2011 were identified from the French National Hospital discharge database. Information on prescription of innovative drugs from an associated database (FICHCOMP) was crossed with the population density of the municipality and a social deprivation index based on national census data. RESULTS: Overall, 21,974 incident cases of metastatic lung cancer were identified, all of whom were followed for 2 years. Of the 11,486 analysable patients receiving chemotherapy in the public sector, 6959 were treated with a FICHCOMP drug at least once, principally pemetrexed. In multivariate analysis, prescription of FICHCOMP drugs was less frequent in patients ≥66 years compared to those ≤55 years (odds ratio: 0.49 [0.44-0.55]), in men compared to women (0.86 [0.79-0.94]) and in patients with renal insufficiency (0.55 [0.41-0.73]) and other comorbidities. Prescription rates were also associated with social deprivation, being lowest in the most deprived municipalities compared to the most privileged municipalities (odds ratio: 0.82 [0.72-0.92]). No association was observed between the population density of the municipality and access to innovative drugs. CONCLUSION: Although access to innovative medication in France seems to be relatively equitable, social deprivation is associated with poorer access. The reasons for this need to be investigated and addressed.

Requests for post-registration studies (PRS), patients follow-up in actual practice: Changes in the role of databases.

Early market access of health products is associated with a larger number of requests for information by the health authorities. Compared with these expectations, the growing expansion of health databases represents an opportunity for responding to questions raised by the authorities. The computerised nature of the health system provides numerous sources of data, and first and foremost medical/administrative databases such as the French National Inter-Scheme Health Insurance Information System (SNIIRAM) database. These databases, although developed for other purposes, have already been used for many years with regard to post-registration studies (PRS). The use thereof will continue to increase with the recent creation of the French National Health Data System (SNDS [2016 health system reform law]). At the same time, other databases are available in France, offering an illustration of "product use under actual practice conditions" by patients and health professionals (cohorts, specific registries, data warehouses, etc.). Based on a preliminary analysis of requests for PRS, approximately two-thirds appeared to have found at least a partial response in existing databases. Using these databases has a number of disadvantages, but also numerous advantages, which are listed. In order to facilitate access and optimise their use, it seemed important to draw up recommendations aiming to facilitate these developments and guarantee the conditions for their technical validity. The recommendations drawn up notably include the need for measures aiming to promote the visibility of research conducted on databases in the field of PRS. Moreover, it seemed worthwhile to promote the interoperability of health data warehouses, to make it possible to match information originating from field studies with information originating from databases, and to develop and share algorithms aiming to identify criteria of interest (proxies). Methodological documents, such as the French National Authority for Health (HAS) recommendations on "Les études post-inscription sur les technologies de santé (médicaments, dispositifs médicaux et actes). Principes et méthodes" [Post-registration studies on health technologies (medicinal products, medical devices and procedures). Principles and methods] should be updated to incorporate these developments.

Hospitalisation costs of metastatic melanoma in France; the MELISSA study (MELanoma In hoSpital coSts Assessment).

BACKGROUND: Management of metastatic melanoma is changing rapidly following the introduction of innovative effective therapies, with consequences for the allocation of healthcare resources. The objective of this study was to assess hospitalisation costs of metastatic melanoma in France from 2011 to 2013 from the perspective of the government payer. METHODS: The population studied corresponded to all adults with metastatic melanoma hospitalised in France between 1st January 2011 and 31st December 2013 who required chemotherapy, immunotherapy or radiotherapy due to tumour progression and unresectable Stage III or Stage IV melanoma. Metastatic melanoma was identified by ICD-10 codes documented in the hospital patient discharge records. For each patient, hospital stays were stratified into a pre- or post- progression health state using proxy variables for the RECIST criteria. All healthcare expenditure documented in the French national hospital claims system database and incurred between the index hospitalisation (or change of progression state) and the end of follow-up were analysed. For the principal analysis, valuation of healthcare resource consumption was performed using official national hospitalisation tariffs. Any expensive therapy administered during the stay was documented from a linked database of expensive drugs (FICHCOMP). RESULTS: Seventy-eight thousand seven hundred fifty hospital stays by 10,337 patients with metastatic melanoma were identified over the three-year study period. Annual per capita costs of hospitalisation were € 5046 in the pre-progression stage and € 19,006 in the post-progression stage. Hospitalisations attributed to adverse drug reactions to chemotherapy or immunotherapy were observed in 27% of patients. Annual per capita costs of these hospitalisations related to adverse drug reactions were € 3762 in the pre-progression stage and € 5523 in the post-progression stage. CONCLUSIONS: Hospitalisation costs related to metastatic melanoma rise substantially as the disease progresses. Treatment strategies which slow down disease progression would be expected to reduce costs of hospitalisation for metastatic melanoma, although they may also entail significant acquisition costs. This will entail organisational changes of resource allocation for the treatment of metastatic melanoma in hospitals.

[Regional differences in hospitalisations for complications of chronic hepatitis C in 2012]. / Disparités régionales des hospitalisations pour complication de l'hépatite chronique C en 2012.

Objective: Only limited recent information is available concerning the regional incidence and prevalence of chronic hepatitis C (CHC), but this information is critical for optimal definition of public health policies for the management of hepatitis C. The objective of this study was to evaluate the feasibility of mapping potential regional differences in the prevalence of CHC and its complications using data from a health administrative database. Methods: The 2012 PMSI MCO hospital database contains information on diagnosis and healthcare resource use, essentially related to all hospitalisations in France. Hospital stays related to CHC were identified on the basis of ICD-10 disease codes. Hospital stays were classified according to stage of liver disease: non-cirrhotic liver disease, compensated cirrhosis, decompensated cirrhosis or hepatocellular carcinoma (HCC). All study variables were documented for each French administrative region in 2012. Results: In 2012, 12,040 patients were hospitalised in France for a reason related to CHC, corresponding to a standardised age- and gender- adjusted prevalence rate of 19.3/100,000 persons. The highest prevalences of CHC and HCC were observed in the Ile de France, Alsace and Provence-Alpes-Côte-d'Azur regions. Conclusions: This study demonstrates the feasibility of using the PMSI database to identify regional differences in the prevalence of CHC. This information may be useful for planning regional healthcare resource provision for CHC.

Burden of stroke and other cardiovascular complications in patients with atrial fibrillation hospitalized in France.

AIMS: Atrial fibrillation (AF) is associated with numerous cardiovascular complications. We sought to estimate the annual burden of cardiovascular complications in AF patients in French hospitals. METHODS AND RESULTS: All AF patients hospitalized in France in 2012 were identified from the national public/private hospital database. Comorbid conditions and medical histories were documented using medical records dating back 5 years. Reasons for hospitalization, type of admission (emergency or otherwise), length of stay, rehabilitation transfers, and death at discharge were identified and costs of acute and rehabilitation care determined (2012 Euros). In total, 533 044 AF patients (mean age ± SD 78.0 ± 11.4 years, 47.1% women) were hospitalized in 2012 for any reason. Hospitalizations were cardiovascular-related in 267 681 patients [22.5% cardiac dysrhythmia, 18.3% heart failure, 7.1% vascular/ischaemic diseases, 6.9% stroke/transient ischaemic attack (TIA)/systemic embolism (SE), and 1.3% haemorrhages]. Patients with stroke/TIA/SE had higher rates of emergency admission (68.1%), transfer to rehabilitation unit (28.1%), and death at discharge (13.7%) than those with other cardiovascular complications, with the exception of haemorrhages, where emergency admission rates were similar. They also had longer mean lengths of stay (12.6 ± 13.2 days for acute care and 46.8 ± 42.5 days for rehabilitation). The annual total cost (acute care and rehabilitation) for all hospitalized cardiovascular events was €1.94 billion, of which heart failure represented €805 million, vascular/ischaemic diseases €386 million, stroke €362 million, cardiac dysrhythmia €341 million, and haemorrhage €48 million. CONCLUSION: Half a million patients with AF were hospitalized in France in 2012. Cardiovascular-related hospitalizations involved half of these admissions, for a global burden of almost €2 billion, equivalent to 2.6% of total expenditure in French hospitals. Among these hospitalizations stroke/TIA/SE represented costly, but potentially preventable, complications.

Progression-free survival, overall survival and quality of life: What is their medicoeconomic importance in oncology?

Medico-economic evaluations estimate, for a given health technology, the added cost and the clinical benefit compared to a reference strategy. The objective here is to analyze the criteria used to measure clinical benefit as the basis for market access and reimbursement decisions for drugs in oncology both in France and in Europe. Prolonged overall survival is the criterion of choice to demonstrate the benefit of an anticancer drug; a survival gain of 2 to 3 months or more would be considered as relevant for a new product versus the comparator. In the absence of survival benefit or mature data on survival, progression-free survival or symptom-free survival and the availability of alternative curative treatments, decrease in drug toxicity and quality of life improvement may be considered. Differences in clinical benefit assessment between regulatory agencies and payers are not specific to France. Case studies show that it is difficult to find a consistency in reimbursement and pricing decisions and to identify factors that may fully explain reimbursement decisions when survival benefit is not demonstrated.

Incidence and cost of stroke and hemorrhage in patients diagnosed with atrial fibrillation in France.

BACKGROUND: Stroke represents a major complication of atrial fibrillation (AF). The current anticoagulation options for stroke prevention increase hemorrhage risk. The objective of the study was to estimate the incidence and costs of hospitalization for stroke and hemorrhage in patients with AF who are eligible for stroke prevention. METHODS: Patients hospitalized for AF were identified from the French National hospital database (Programme Médicalisé des Systèmes d'Information) and a calculated stroke risk score (congestive heart failure, hypertension [blood pressure consistently >140/90 mm Hg], age ≥75 years, diabetes mellitus, and previous stroke, transient ischemic attack [CHADS2]). Adult patients eligible for stroke prevention (CHADS2 >0) were enrolled. The incidence of hospitalization for stroke and hemorrhage was calculated over a 2-year period. Costs of acute care were determined using diagnosis related groups (DRGs) and corresponding National Hospital Tariffs. Rehabilitation costs were analyzed for patients with strokes and classified by stroke severity. RESULTS: Sixty-one thousand five hundred eighty-two patients were identified with a mean age of 75.0 ± 11.0 years and a mean CHADS2 score of 1.90 ± 0.99. The 24-month cumulative incidence of any stroke was 32.1 cases/1,000 patients with AF (ischemic, 60%; hemorrhagic, 24%; unspecified, 16%), and that of hemorrhage was 53.1 cases/1,000 patients with AF (gastrointestinal, 26%; intracranial, 5%; other, 69%). The mean costs of ischemic and hemorrhagic strokes were €4,848 and €7,183 (mild), €10,909 and €14,298 (moderate), €29,065 and €29,701 (severe), and €6,035 and €4,590 (fatal), respectively. The mean costs of hemorrhage by type were €3,601 (gastrointestinal), €7,331 (intracranial), €3,941 (other major), and €2,552 (nonmajor). CONCLUSIONS: The incidence and cost of hospitalization for hemorrhage should be considered in the global burden of AF. These data should be useful for pharmacoeconomic evaluation of new oral anticoagulant medications. Such real-world studies may be relevant for monitoring mid- to long-term morbidity and mortality in the AF population.

Real-World Treatment Patterns and Effectiveness of Patients With Advanced Renal Cell Carcinoma: A Nationwide Observational Study.

BACKGROUND: Treatment landscape for advanced renal cell carcinoma (aRCC) has evolved quickly and few data about the real-world treatment patterns are available. This study aimed at describing the real-world treatment patterns and effectiveness of all systemic treatments available for aRCC in first and second-line treatment. MATERIALS AND METHODS: A cohort of patients initiating a first-line systemic treatment for aRCC in 2016 was extracted from the French nationwide healthcare insurance system database (SNDS). The first-line treatment initiation date constituted the index date and patients were followed until death, loss to follow-up, or December 31, 2019, whichever occurred first. aRCC was identified using hospital diagnosis, long-term disease, or renal biopsy before index date. All analyses were performed for first and second-line treatment. Overall survival (OS) and time-to-next treatment or death (TNT-D) were estimated using Kaplan-Meier approach. RESULTS: In 2016, 1629 patients initiated a first-line treatment for aRCC. Most of them were male (75.9%) and the median age was 67 years. Most of patients (91.7%) had received a tyrosine kinase inhibitor as first-line treatment, mainly sunitinib (64.4%), and 53.5% received a second-line, among which 43.7% nivolumab. Median OS (95% confidence interval [CI]) was 20.7 (95% CI:18.2-22.4) months from first-line treatment initiation and 15.4 (13.9-17.5) months from second-line treatment initiation. Median TNT-D were respectively 9.3 (9.7-12.1) months and 6.9 (5.9-7.7) months. CONCLUSION: This study highlights the limited survival of aRCC patients These results provide a valuable baseline and highlight the need for innovation, such as immune checkpoint inhibitor-based combinations that have recently became first-line standard of care.

[Hypoglycemic treatment in type 2 diabetes patients suffering from moderate to severe renal failure in France. Aim of the study]. / Traitements antidiabétiques des patients diabétiques de type 2 atteints d'une insuffisance rénale modérée ou sévère suivis en médecine générale en France.

UNLABELLED: The purpose of this study is to describe the hypoglycemic agents prescribed to type 2 diabetes patients (T2D) with renal impairment (RI). METHOD: Data were extracted from the database LPD-CEGEDIM, based on a sample of 1200 general practitioners. The analysis focused on T2D patients with RI, defined by a glomerular filtration rate (GFR) below 60 mL/min/1.73 m², estimated by the MDRD formula. RESULTS: Of the 36 255 patients identified with T2D, a GFR was calculated for 8 647 patients (23.9%), 1 472 (22%) with a moderate RI (GFR=[30mL/min/1.73 m²-60mL/min/1.73 m²]) and 86 (1.0%) with a severe RI (GFR=[15mL/min/1.73 m-30mL/min/1.73 m²]); 47,6% of T2D patients with a moderate RI and 52,3% of T2D patients with a severe RI were treated with at least one drug contraindicated in patients with moderate or severe RI. CONCLUSION: These findings suggest better informing doctors of these contraindications and show the value of having new hypoglycemic drugs that can be used in case of RI.

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.

Organizational Impact of Immunotherapies in Advanced Cancers in France.

PURPOSE: In 2020, the French National Authority for Health (Haute Autorité de Santé) published a methodologic guide called organizational impact (OI) cartography to define and structure assessment of the OI of health technologies. As immunotherapies are associated with extended survival and improved quality of life in advanced cancer, we aimed to identify OIs that immunotherapies had on health care systems and professionals. To our knowledge, we suggest the first implementation for OI assessment on the basis of the cartography. METHODS: A literature review was conducted, and interviews with health care professionals (HCPs) were performed to identify OIs of immunotherapies. They were asked if immunotherapies had OIs classified into three macrocriteria, namely, impact on the care process (six criteria), impact on capacities and skills required (six criteria), and impact on society (four criteria). If an OI was mentioned for a criterion, information on its impact (minor/moderate/major) and its timing was collected. We considered that an OI existed when 75% of HCPs mentioned an impact for a given criterion. RESULTS: Overall, 27 HCPs were interviewed. For 12 of 16 criteria, most HCPs mentioned an impact, whereas the literature identified impacts for 11 criteria. Four criteria (skills and transfer between HCPs, scheduling capabilities, and social relationship) had consensus among HCPs and a high impact; two criteria (rhythm or care duration, working/living conditions) showed consensus but a moderate impact; two criteria (funding and scheduling capabilities cross-structure) had a high impact but no consensus. For eight criteria (as environment or inequity), there was no consensus and moderate impact. CONCLUSION: The introduction of immunotherapies for advanced cancer has had an important OI in France, regarding capacities and skills. Further research using qualitative analysis of interviews will provide more information regarding OI.

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.

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.

Machine Learning-Based Analysis of Treatment Sequences Typology in Advanced Non-Small-Cell Lung Cancer Long-Term Survivors Treated With Nivolumab.

PURPOSE: Immune checkpoint inhibitors substantially changed advanced non-small-cell lung cancer (aNSCLC) management and can lead to long-term survival. The aims of this study were (1) to use a machine learning method to establish a typology of treatment sequences on patients with aNSCLC who were alive 2 years after initiating a treatment with anti-programmed death-ligand 1 monoclonal antibody nivolumab and (2) to describe the patients' characteristics according to the typology of treatment sequences. MATERIALS AND METHODS: This retrospective observational study was based on data from the comprehensive French hospital discharge database for all patients with lung cancer with at least one line of platinum-based chemotherapy, starting nivolumab between January 1, 2015, and December 31, 2016, and alive 2 years after nivolumab treatment initiation. Patients were followed until December 31, 2018. A typology of most common treatment sequences was established using hierarchical clustering with time sequence analysis. RESULTS: Two thousand two hundred twelve study patients were, on average, 63.0 years old, 69.9% of them were men, and 61.9% had a nonsquamous cell carcinoma. During the 2 years after nivolumab treatment initiation, clusters of patients with four basic types of treatment sequences were identified: (1) almost continuous nivolumab treatment (44% of patients); (2) nivolumab most of the time followed by a treatment-free interval or a chemotherapy (15% of patients); and a short or medium nivolumab treatment, followed by (3) a long systemic treatment-free interval (17% of patients) or (4) a long chemotherapy (23% of patients). CONCLUSION: This machine learning approach enabled the identification of a typology of four representative treatment sequences observed in long-term survival. It was noted that most long-term survivors were treated with nivolumab for well over 1 year.