Avelumab as second-line or later treatment in patients with metastatic Merkel cell carcinoma: Analysis of real-world outcomes in France using the CARADERM database linked to the French national healthcare database.

AIM: Avelumab has been approved worldwide for treatment of metastatic Merkel cell carcinoma (mMCC), a rare and aggressive skin cancer. This study evaluated outcomes in patients with mMCC in France who received avelumab as second-line or later (2L+) treatment in routine clinical practice. METHODS: This retrospective, noninterventional study evaluated all patients diagnosed with mMCC using two databases: CARADERM (French national database of rare dermatological cancers) and SNDS (national healthcare database), identified via probabilistic linkage. Eligible patients initiated avelumab as 2L+ treatment between August 2016 and December 2019 and were followed for 24 months. The primary endpoint was overall survival (OS) at 24 months. RESULTS: Overall, 180 patients who received 2L+ avelumab were identified (112 from CARADERM, 68 after SNDS linkage). Median age at diagnosis was 74.0 years and 177 (98.3 %) had received chemotherapy alone as first-line treatment. Median follow-up was 13.1 months. Median OS from start of avelumab was 14.6 months (95 % CI, 9.9-21.3) in the overall population, 15.9 months (95 % CI, 8.6-28.3) in CARADERM patients, and 13.3 months (95 % CI, 6.7-19.1) in non-CARADERM patients. OS rates at 12 and 24 months were 53.8 % (95 % CI, 46.2 %-60.8 %) and 40.5 % (95 % CI, 33.2 %-47.6 %), respectively. In evaluable patients (CARADERM database), median progression-free survival was 3.6 months (95 % CI, 2.7-7.5) and the objective response rate was 55.3 % (95 % CI, 45.3-65.4), including complete response in 31.9 %. CONCLUSIONS: Real-world outcomes with 2L+ avelumab treatment for mMCC are consistent with clinical trial findings, supporting the recommendation of avelumab as a standard of care.

Treatment sequence of first and second generation tyrosine kinase inhibitor followed by osimertinib in EGFR-mutated non-small-cell lung cancer: a real life study.

Background: We aimed to assess the effectiveness and cost of patients with first line tyrosine kinase inhibitors (TKIs) sequence of first (1G) and second generation (2G) followed by osimertinib. Materials & methods: Using the French nationwide claims and hospitalization database, we analyzed non-small-cell lung cancer patients who had been treated with osimertinib between April 2015 and December 2017, after a first line treatment with a TKI-1G/2G. Results: The median time on treatment for sequential TKI-1G/2G followed by osimertinib was 34 months (95% CI: 31-46); 13 and 12months, respectively for TKI 1G or 2G and TKI 3G, respectively. The median overall survival for sequential TKI 1G or 2G followed by osimertinib was 37 months (95% CI: 34-42). The mean monthly costs per patient was €5162. Conclusion: These results, in line with those observed during clinical trials, confirm the effectiveness of the sequence TKI-1G/2G followed by osimertinib in EGFR-mutated non-small-cell lung cancer.

Health economic evaluation in idiopathic pulmonary fibrosis in France.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive, fibrosing interstitial pneumonia of unknown cause. To date, there is no specific cure for IPF, and only two treatments (pirfenidone and nintedanib) have marketing authorizations and recommendations in international and French guidelines. OBJECTIVES: A cost-utility analysis (CUA) has been conducted to evaluate the efficiency of nintedanib, in comparison to all available alternatives, in a French setting using the official methodological guidelines. METHODS: A previously developed lifetime Markov model was adapted to the French setting by simulating the progression of IPF patients in terms of lung function decline, incidence of acute exacerbations, and death. Considering the effect of IPF on patients' quality-of-life, a CUA integrating quality adjusted life years (QALY) was chosen as the primary outcome measure in the main analysis. One-way, probabilistic, and scenario sensitivity analyses were performed to evaluate the robustness of the model. RESULTS: Treatment with nintedanib resulted in an estimated total cost of €76,414 (vs €82,665 for pirfenidone). In comparison with all other available options, nintedanib was predicted to provide the most QALY gained (3.34 vs 3.29). This analysis suggests that nintedanib has a 59.0% chance of being more effective than pirfenidone and s 77.3% chance of being cheaper than pirfenidone. Sensitivity analyses showed the results of the CUA to be robust. CONCLUSIONS: In conclusion, this CUA has found that nintedanib appears to be a more cost-effective therapeutic option than pirfenidone in a French setting, due to fewer acute exacerbations and a better tolerability profile.

Evaluating the cost-effectiveness of afatinib after platinum-based therapy for the treatment of squamous non-small-cell lung cancer in France.

BACKGROUND AND AIMS: Lung cancer has the highest mortality rate of all cancers worldwide. Non-small-cell lung cancer (NSCLC) accounts for 85% of all lung cancers and has an extremely poor prognosis. Afatinib is an irreversible ErbB family blocker designed to suppress cellular signaling and inhibit cellular growth and is approved in Europe after platinum-based therapy for squamous NSCLC. The objective of the present analysis was to evaluate the cost-effectiveness of afatinib after platinum-based therapy for squamous NSCLC in France. METHODS: The study population was based on the LUX-Lung 8 trial that compared afatinib with erlotinib in patients with squamous NSCLC. The analysis was performed from the perspective of all health care funders and affected patients. A partitioned survival model was developed to evaluate cost-effectiveness based on progression-free survival and overall survival in the trial. Life expectancy, quality-adjusted life expectancy and direct costs were evaluated over a 10-year time horizon. Future costs and clinical benefits were discounted at 4% annually. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: Model projections indicated that afatinib was associated with greater life expectancy (0.16 years) and quality-adjusted life expectancy (0.094 quality-adjusted life years [QALYs]) than that projected for erlotinib. The total cost of treatment over a 10-year time horizon was higher for afatinib than erlotinib, EUR12,364 versus EUR9,510, leading to an incremental cost-effectiveness ratio of EUR30,277 per QALY gained for afatinib versus erlotinib. Sensitivity analyses showed that the base case findings were stable under variation of a range of model inputs. CONCLUSION: Based on data from the LUX-Lung 8 trial, afatinib was projected to improve clinical outcomes versus erlotinib, with a 97% probability of being cost-effective assuming a willingness to pay of EUR70,000 per QALY gained, after platinum-based therapy in patients with squamous NSCLC in France.

Cost-Effectiveness Analysis of Afatinib versus Gefitinib for First-Line Treatment of Advanced EGFR-Mutated Advanced Non-Small Cell Lung Cancers.

INTRODUCTION: The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor gefitinib were compared in the multicenter, international, randomized, head-to-head phase 2b LUX-Lung 7 trial for first-line treatment of advanced EGFR mutation-positive NSCLCs. Afatinib and gefitinib costs and patients' outcomes in France were assessed. METHODS: A partitioned survival model was designed to assess the cost-effectiveness of afatinib versus gefitinib for EGFR mutation-positive NSCLCs. Outcomes and safety were taken primarily from the LUX-Lung 7 trial. Resource use and utilities were derived from that trial, an expert-panel questionnaire, and published literature, limiting expenditures to direct costs. Incremental cost-effectiveness ratios (ICERs) were calculated over a 10-year time horizon for the entire population, and EGFR exon 19 deletion or exon 21 L858R mutation (L858R) subgroups. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: For all EGFR mutation-positive NSCLCs, the afatinib-versus-gefitinib ICER of was €45,211 per quality-adjusted life-year (QALY) (0.170 QALY gain for an incremental cost of €7697). ICERs for EGFR exon 19 deletion and L858R populations were €38,970 and €52,518, respectively. Afatinib had 100% probability to be cost-effective at a willingness-to-pay threshold of €70,000/QALY for patients with common EGFR mutations. CONCLUSION: First-line afatinib appears cost-effective compared with gefitinib for patients with EGFR mutation-positive NSCLCs.

Implementación de una iniciativa para promover un entorno laboral saludable en un Servicio de Medicina Familiar de un Hospital Universitario: investigación-acción participativa / Implementation of an initiative to promote a healthy working environment in a Division of Family Medicine at a University Hospital: participatory action research

Objetivos: describir el proceso y los resultados de la implementación de un proyecto para la promoción de un entorno laboral saludable (ELS) en el Servicio de Medicina Familiar y Comunitaria de un Hospital Universitario. Métodos: investigación con enfoque cualitativo, diseño investigación-acción participativa desarrollada entre marzo de 2011 y marzo de 2012. La intervención incluyó tres ejes de trabajo (alimentación, actividad física y estrategias comunicacionales) y estuvo dirigida a 60 profesionales médicos y a los cuatro empleados administrativos de dicho servicio. Se proveyeron cuestionarios (adaptados del "STEP" propuesto por la Organización Mundial de la Salud) antes de iniciar el proyecto y al año de la intervención. Se realizaron entrevistas semiestructuradas y se aplicaron técnicas de observación-participante. Resultados: el proyecto se institucionalizó y se destacó su repercusión positiva en el clima laboral. Se instauró dentro del Servicio, durante el horario de trabajo, el consumo de frutas y las pausas activas, se generaron espacios de actividad física y de recreación deportiva en horarios extralaborales y se difundió su existencia a otros sectores del hospital. Se documentó un aumento estadísticamente significativo en el consumo semanal promedio de frutas (+3,04 porciones semanales; IC 95% 0,86 a 5,21; p < 0,01) y un aumento estadísticamente no significativo en el consumo semanal de hortalizas (+0,8 porciones semanales; IC 95%: -1,84 a 3,45; p = 0,55) y en la práctica semanal de ejercicio (+101 minutos; -78,7 a 281,55; p = 0,27). Conclusiones: una intervención sencilla y sustentable contribuyó a instalar el consumo de frutas durante el horario laboral y la posibilidad de la pausa activa; asimismo generó en las redes sociales un espacio de intercambio para propuestas saludables. Esperamos que estos resultados motiven a otros grupos de trabajo a avanzar en programas que promuevan un ELS. (AU)

Objectives: To describe the process and the results of the implementation of a project to promote a healthy working environment (HWE) in the Division of Family and Community Medicine at a University Hospital. Methods: Qualitative research using part of a participatory action research conducted between March 2011 and March 2012. The intervention included three working areas (food, physical activity and communication strategies) and was directed to 60 medical professionals and four administrative employees that were working in that service. Questionnaires (adapted from "STEP" proposed by the World Health Organization) have been administered before starting the project and a year of intervention. Semi-structured interviews and participant observation techniques were performed. Results: the project was institutionalized, what highlights its positive impact on the working environment. Consumption of fruits and active breaks during working hours was installed and physical activity/recreative sports spaces during extra-working hours were generated and spread to other divisions of the hospital. After the program a statistically significant increase (+3,04 portions weekly; 95% CI 0.86 to 5.21; p < 0.01) in the weekly average fruit consumption was documented and a no statistically significant increase in the weekly consumption of vegetables (+0.8 weekly servings, 95%CI -1.84 to 3.45; p = 0.55) and in weekly exercise (+101 min; -78.7 to 281.55; p = 0.27). Conclusions: A simple and sustainable intervention contributed to installed fruit consumption during working hours, the possibility of active pause and generates a social networking space for healthy exchange proposals. We hope these results will encourage other working groups to implement programs that promote HWE. (AU)