Clinical benefit of anti-PD-(L)1 immunotherapies in advanced cancer in France: a population-based estimate from 2014 to 2021.

BACKGROUND: In France, the potential benefit of new treatments is initially evaluated by the Haute Autorité de Santé to determine reimbursement and pricing, but rarely afterwards. Although immunotherapies (ITs) have considerably improved the survival of patients, few data are available on their long-term benefit at a population-treated level. The present retrospective study aimed to assess the clinical benefit of ITs compared to the previous standards of care (SoCs) in France from 2014 to 2021. MATERIALS AND METHODS: To do this, we analyzed all ITs from the anti-programmed cell death protein 1/programmed death-ligand 1 [anti-PD-(L)1] class used in monotherapy or in association with another treatment available in early access or reimbursed in France between 2014 and 2021, regardless of indication. The number of patients initiating an IT was retrieved by year, drug and indication. Using extrapolated Kaplan-Meier curves, utility scores and the population treated, the clinical benefit was expressed as the number of deaths prevented (DP), life-years (LYs) and quality-adjusted life years (QALYs) gained compared to previous SoC. RESULTS: Across the period, five ITs were marketed in 21 indications related to eight primary tumor sites. Between 2014 and 2021, 132 924 patients initiated an IT. By December 2021, 16 173 (13 804-17 141) deaths were delayed compared to previous SoC, mainly in lung cancer. Compared to their SoC, ITs provided a gain of 37 316 (33 581-41 048) additional LYs and 27 709 (23 784-30 450) additional QALYs. Lung cancer was the driver indication with 70.6% of LYs and 68.4% of QALYs gained followed by melanoma with 18.7% and 20.4% of the gain, respectively. CONCLUSIONS: Significant gains in DP, LYs and QALYs have been observed in France following the introduction of ITs.

Stroke prevention in patients with atrial fibrillation in France: comparative cost-effectiveness of new oral anticoagulants (apixaban, dabigatran, and rivaroxaban), warfarin, and aspirin.

OBJECTIVES: To conduct an economic evaluation of the currently prescribed treatments for stroke prevention in patients with non-valvular atrial fibrillation (NVAF) including warfarin, aspirin, and novel oral anticoagulants (NOACs) from a French payer perspective. METHODS: A previously published Markov model was adapted in accordance to the new French guidelines of the Commission for Economic Evaluation and Public Health (CEESP), to adopt the recommended efficiency frontier approach. A cohort of patients with NVAF eligible for stroke preventive treatment was simulated over lifetime. Clinical events modeled included strokes, systemic embolism, intracranial hemorrhage, other major bleeds, clinically relevant non-major bleeds, and myocardial infarction. Efficacy and bleeding data for warfarin, apixaban, and aspirin were obtained from ARISTOTLE and AVERROES trials, whilst efficacy data for other NOACs were from published indirect comparisons. Acute medical costs were obtained from a dedicated analysis of the French national hospitalization database (PMSI). Long-term medical costs and utility data were derived from the literature. Univariate and probabilistic sensitivity analyses were performed to assess the robustness of the model projections. RESULTS: Warfarin and apixaban were the two optimal treatment choices, as the other five treatment strategies including aspirin, dabigatran 110 mg, dabigatran in sequential dosages, dabigatran 150 mg, and rivaroxaban were strictly dominated on the efficiency frontier. Further, apixaban was a cost-effective alternative vs warfarin with an incremental cost of €2314 and an incremental quality-adjusted life year (QALY) of 0.189, corresponding to an incremental cost-effectiveness ratio (ICER) of €12,227/QALY. CONCLUSIONS: Apixaban may be the most economically efficient alternative to warfarin in NVAF patients eligible for stroke prevention in France. All other strategies were dominated, yielding apixaban as a less costly yet more effective treatment alternative. As formally requested by the CEESP, these results need to be verified in a French clinical setting using stroke reduction and bleeding safety observed in real-life patient cohorts using these anticoagulants.

Burden of breast cancer with brain metastasis: a French national hospital database analysis.

OBJECTIVE: Incidence of breast cancer with brain metastases (BCBM) is increasing, especially among patients over-expressing HER2. Epidemiology on this sub-type of cancer is scarce, since cancer registries carry no information on the HER2 status. A retrospective database analysis was conducted to estimate the burden of BCBM, especially among HER2-positive patients in a secondary objective. METHODS: Patients with a new diagnosis of BCBM carried out between January and December 2008 were identified from the national hospital database using the International Disease Classification. Patients receiving a targeted anti-HER2 therapy were identified from the national pharmacy database. Hospital and pharmacy claims were linked to estimate the burden of HER2-positive patients. Data on hospitalizations were extracted to describe treatment patterns and healthcare costs during a 1-year follow-up. Predictors of treatment cost were analyzed through multi-linear regression analysis. RESULTS: Two thousand and ninety-nine BCBM patients were identified (mean age (SD) = 57.8 (13.6)), of whom 12.2% received a targeted anti-HER2 therapy; 79% of patients had brain metastases associated with extracranial metastases, and the attrition rate reached 82%. Patients received mostly palliative care (47.4%), general medical care (40.6%), and chemotherapy (35.0%). The total annual hospital cost of treatment was 8,426,392€, representing a mean cost of 22,591€ (±14,726) per patient, mainly influenced by extracranial metastases, surgical acts, and HER2-overexpression (p < 0.0001). CONCLUSIONS: The database linkage of hospital and pharmacy claims is a relevant approach to identify sub-type of cancer. Chemotherapy was widely used as a systemic treatment for breast cancer rather than for local treatment of brain metastases whose morbi-mortality remains high. The variability of treatment costs suggests clinical heterogeneity and, thus, extensive individualization of protocols.