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.

Whole exome sequencing in molecular diagnostics of cancer decreases over time: evidence from a cost analysis in the French setting.

OBJECTIVES: Although high-throughput sequencing is revolutionising medicine, data on the actual cost of whole exome sequencing (WES) applications are needed. We aimed at assessing the cost of WES at a French cancer institute in 2015 and 2018. METHODS: Actual costs of WES application in oncology research were determined using both micro-costing and gross-costing for the years 2015 and 2018, before and after the acquisition of a new sequencer. The entire workflow process of a WES test was tracked, and the number and unit price of each resource were identified at the most detailed level, from library preparation to bioinformatics analyses. In addition, we conducted an ad hoc analysis of the bioinformatics storage costs of data issued from WES analyses. RESULTS: The cost of WES has decreased substantially, from €1921 per sample (i.e. cost of €3842 per patient) in 2015 to €804 per sample (i.e. cost of €1,608 per patient) in 2018, representing a decrease of 58%. In the meantime, the cost of bioinformatics storage has increased from €19,836 to €200,711. CONCLUSION: This study suggests that WES cost has decreased significantly in recent years. WES has become affordable, even though clinical utility and efficiency still need to be confirmed.

Partial versus whole breast irradiation: Side effects, patient satisfaction and costs.

PURPOSE: Since accelerated partial breast irradiation has demonstrated non-inferiority to whole breast irradiation regarding recurrence rate in patients with early stage breast cancer, our objective was to compare its impact on short-term adverse events, patient satisfaction and costs. MATERIALS AND METHODS: Patients with early stage breast cancer treated by breast-conserving surgery between 2007 and 2012 were included: 48 women who received three-dimensional conformal accelerated partial breast irradiation in a multicentre phase-II trial were paired with 48 patients prospectively treated with whole breast irradiation. Adverse events, and patients' opinions concerning cosmesis, satisfaction and pain, were gathered 1 month after treatment. Direct and indirect costs were collected from the French National Health Insurance System perspective until the end of radiotherapy. RESULTS: When comparing its impact, skin reactions occurred in 37% of patients receiving three-dimensional conformal accelerated partial breast radiotherapy and 60% of patients receiving whole breast irradiation (P=0.07); 98% were very satisfied in the group three-dimensional conformal accelerated partial breast radiotherapy versus 46% in the group treated with whole breast irradiation (P<0.001); direct costs were significantly lower in the group treated with partial breast irradiation (mean cost: 2510€ versus 5479€/patient), due to less radiation sessions. CONCLUSION: In patients with early-stage breast cancer, partial irradiation offered a good alternative to whole breast irradiation, as it was less expensive and satisfactory. These, and the clinical safety and tolerance results, need to be confirmed by long-term accelerated partial breast irradiation results in on-going phase III trials.

Update of survival and cost of metastatic melanoma with new drugs: Estimations from the MelBase cohort.

PURPOSE: Since 2011, significant progress was observed in metastatic melanoma (MM), with the commercialisation of seven immunotherapies or targeted therapies, which showed significant improvement in survival. In France, in 2004, the cost of MM was estimated at €1634 per patient; this cost has not been re-estimated since. This study provided an update on survival and cost in real-life clinical practice. METHODS: Clinical and economic data (treatments, hospitalisations, radiotherapy sessions, visits, imaging and biological exams) were extracted from the prospective MelBase cohort, collecting individual data in 955 patients in 26 hospitals, from diagnosis of metastatic disease until death. Survival was estimated by the Kaplan-Meier method. Costs were calculated from the health insurance perspective using French tariffs. For live patients, survival and costs were extrapolated using a multistate model, describing the 5-year course of the disease according to patient prognostic factors and number of treatment lines. RESULTS: Since the availability of new drugs, the mean survival time of MM patients has increased to 23.6 months (95%confidence interval [CI] :21.2;26.6), with 58% of patients receiving a second line of treatment. Mean management costs increased to €269,682 (95%CI:244,196;304,916) per patient. Drugs accounted for 80% of the total cost. CONCLUSION: This study is the first that evaluated the impact of immunotherapies and targeted therapies both on survival and cost in real-life conditions. Alongside the introduction of breakthrough therapies in the first and subsequent lines, MM has been associated with a significant increase in survival but also in costs, raising the question of financial sustainability.

Update on the treatment of non-small-cell lung cancer: focus on the cost-effectiveness of new agents.

BACKGROUND: The incidence of lung cancer and the cost of drug treatment have increased dramatically in the last decade. This article examines the costs of new target agents, such as tyrosine kinase inhibitors (TKIs) and anti-angiogenic drugs. METHODS: This study uses PubMed research to focus on the topics of lung cancer, economics, and new targeted therapies. RESULTS: The published papers only addressed TKIs and anti-angiogenic antibodies. For gefitinib, the results favored a clinical-based selection, despite the low number of studies. Erlotinib was studied in second line and as a maintenance treatment (with the studies reaching opposite conclusions in terms of cost-effectiveness). Economic analyses were not in favor of bevacizumab, but the studies on this topic were very heterogeneous. CONCLUSION: The economic impact of a drug depends on the health care system organization. Future clinical trials must include economic analyses, particularly with TKIs in the first line.

Safety and quality assurance of chemotherapeutic preparations in a hospital production unit: acceptance sampling plan and economic impact.

OBJECTIVE: The opportunity to apply a sampling plan was evaluated. Costs were computed by a microcosting study. SETTING: In 2003, a sampling plan was defined to reduce the number of chemotherapy quality controls while preserving the same level of quality. Recent qualitative and quantitative changes led us to define a second sampling plan supplemented by an economic evaluation to determine the cost and cost-savings of quality control. METHODS: The study considers preparation produced during four semesters classified into three groups. The first one includes drugs produced below 200 batches a semester. Group 2, those for which the lot of preparation lots would have been rejected twice among these four semesters. Group 3, those would have been accepted (≥3 'acceptable lot'). A single sampling plan by attributes was applied to this group with an acceptance quality level of 1.65% and a lot tolerance percent defective below 5%. A micro-costing study was conducted on quality control, from the sampling to the validation of the results. RESULTS: Among 39 cytotoxic drugs, 11 were sampled which enabled to avoid a mean of 17,512 control assays per year. Each batch of the 28 non-sampled drugs was however analyzed. Costs were estimated at 2.98€ and 5.25€ for control assays depending of the analytical method. The savings from the application of the sampling plans was 153,207€ in 6 years. CONCLUSION: The sampling plan allowed maintaining constancy in number of controls and the level of quality with significant costsavings, despite a substantial increase in drugs to assay and in the number of preparations produced.

Cost-effectiveness of three strategies for second-line erlotinib initiation in nonsmall-cell lung cancer: the ERMETIC study part 3.

Several clinical and biological parameters are known to influence the efficacy of second-line erlotinib therapy for nonsmall cell lung cancer (NSCLC), but their medico-economic impact has not been evaluated. The objective of this study was to compare the incremental cost-effectiveness ratios of strategies for second-line erlotinib initiation in NSCLC: clinically guided initiation (nonsmoking females with adenocarcinoma received erlotinib; all other patients received docetaxel) and biologically guided selection (patients with epidermal growth factor receptor (EGFR) mutation received erlotinib; patients with wild-type EGFR or unknown status received docetaxel), compared with initiation with no patient selection (strategy reference). A Markov model was constructed. Outcomes (overall and progression-free survival), transition probabilities and direct medical costs (from the French third-party payer's perspective) were prospectively collected for individual patients treated with either erlotinib or docetaxel, from treatment initiation to disease progression. Published data were used to estimate utilities and post-progression costs. Sensitivity analyses were performed. The biologically and clinically guided strategies were both more efficient (incremental quality-adjusted life-yrs equal to 0.080 and 0.081, respectively) and less expensive (cost decrease equal to €5,020 and €5,815, respectively) than the no-selection strategy, and the biologically guided strategy was slightly less expensive than the clinically guided strategy. Sensitivity analyses confirmed the robustness of the results. The cost-effectiveness of second-line NSCLC treatment is improved when patients are selected on either clinical or biological grounds.

Economic burden of HPV-related cancers in France.

Human papillomavirus (HPV) infection is associated with a range of diseases and cancers at different anatomical sites. In addition to its role as a necessary cause of cervical cancer, HPV is also associated with cancers of the vulva, vagina, anus, penis, head and neck. With the exception of cervical cancer, however, very few data are available on the economic burden of HPV-associated cancers. We assessed the annual costs associated with management of HPV-related cancers in France from the healthcare payers' perspective. We used data from studies that employed similar methodologies to estimate the costs during 2006 for cervical cancer, vulvar and vaginal cancers, anal cancer, and penile cancer, and during 2007 for head and neck cancers. Data on hospital-management costs for cancer were derived from the French national hospital database. The costs of outpatient care and daily allowance costs were estimated using data from the French National Institute of Cancer report for 2007. The costs for HPV-related cancers were estimated according to the percentage of each cancer type attributable to HPV infection. The estimated total costs associated with HPV-related cancers in France were €239.7 million. The overall costs in men were €107.2 million, driven mainly by head and neck cancers (€94.6 million). The total costs in women were €132.5 million, due mainly to invasive cervical cancer (€83.9 million). The costs associated with HPV-related cancers are important to consider when evaluating the overall benefits of HPV vaccination in males and females.

[Comprehensive geriatric assessment and complications after resection for lung cancer]. / Evaluation gériatrique et morbidité après exérèse pulmonaire pour cancer bronchique.

BACKGROUND: With the expanding elderly population comes an increasing prevalence of lung cancer. Surgery remains the mainstay of treatment for early-stage non-small cell lung cancer. Standard treatment strategies have mostly been validated in young adults. Curative resection is feasible in older patients but careful preoperative evaluation is needed, taking into account the physiologic changes that occur with ageing. A tool used by geriatricians, a comprehensive geriatric assessment, can contribute to our understanding of physiologic age through an evaluation of prognostic factors that are independent predictors of morbidity. PATIENTS: Study 08-05 of the French Lung Oncology Group is a prospective, national, multicentre study. All patients aged over 70 years with a suspicion of lung cancer, receiving curative lung resection, will be included. After inclusion, a comprehensive geriatric assessment (evaluating such diverse areas as functional status, nutritional status, cognition, psychological functioning, and social support) will be performed. The primary outcome is the value of the comprehensive geriatric assessment in predicting the risk of post-operative complications after lung resection for cancer. Post-operative morbidity at 30-days after pulmonary resection will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. The follow-up period is one year. EXPECTED RESULTS: This global assessment may help to initiate specific care plans for the management of lung cancer in the elderly.

[Biosimilars and medico-economic aspects]. / Biosimilaires et facteurs médico-économiques.

Although few molecules are available, annual total sales of biotechnology drugs amounted 71 billion $ in 2008) and knew a 17% progression per year. As traditional drugs had their generic, many biotechnology drugs had or will lose their patent and be copied, called "biosimilars" or "follows-on". According to the economic impact of biotechnology drugs, the availability of biosimilars may result in great reduction of drugs expenditure. In 2004, EMEA has set up specific rules for biosimilars, distinct from those applied to generic drugs, based on clinical research requirement and post-authorization follow-up of these drugs, and then significantly impacting on their costs of research, development and marketing. The economy generated by the availability of biosimilars should be lower than expected, even null, contrasting with those usually generated by generics. In order to better understand the medico-economic factors related to biosimilars availability, this article will described the market of the biotechnology drugs. The differences existing between generics and biosimilars and their impact on costs will be presented. Finally, it will focus on the factors that may facilitate or limit the biosimilars development and their substitution.

Length and cost of hospital stay of radioiodine ablation in thyroid cancer patients: comparison between preparation with thyroid hormone withdrawal and thyrogen.

PURPOSE: Treatment of thyroid cancer consists of thyroidectomy and radioiodine ablation following thyroid-stimulating hormone (TSH) stimulation. Similar ablation rates were obtained with either thyroid hormone withdrawal (THW) or rhTSH. But with rhTSH, the elimination of radioiodine is more rapid, thus reducing its whole-body retention and potentially resulting in a shorter hospital stay. The aim of this study was to assess the financial impact of a reduced length of hospital stay with the use of rhTSH. METHODS: This was a case-control study of thyroid cancer patients treated postoperatively with 3,700 MBq (100 mCi) radioiodine; 35 patients who received rhTSH were matched with 64 patients submitted to THW according to covariates influencing radioiodine retention. The length of hospitalization (LOH) was estimated for each method according to the threshold of radioiodine retention below which the patient can be discharged from the hospital. The economic analysis was conducted from a hospital perspective. Simulations were performed. RESULTS: For a threshold of 400 MBq, the LOH was 2.4 days and 3.5 days with rhTSH and THW, respectively, and the cost for an ablation stay was, respectively, 2,146 and 1,807 . In the French context, 57% of the acquisition cost of rhTSH was compensated by the reduction of the length of hospitalization. CONCLUSION: By increasing the iodine excretion, rhTSH allows a shorter hospitalization length, which partially compensates its acquisition cost.

Sick leave for follow-up control in thyroid cancer patients: comparison between stimulation with Thyrogen and thyroid hormone withdrawal.

INTRODUCTION: The clinical benefits of recombinant human thyroid-stimulating hormone (rhTSH; Thyrogen) are well established as an alternative stimulation procedure to thyroid hormone withdrawal in the diagnostic follow-up of thyroid cancer patients. By avoiding periods of hypothyroidism, patients do not suffer from a decreased quality of life and keep their ability to work. This study compared the frequency, the duration and the cost of sick leave for follow-up control between rhTSH and withdrawal. METHODS: The study population consisted of patients with thyroid carcinoma first treated by thyroidectomy and radioiodine ablation. Patients were recruited at their control visit between October 2004 and May 2006 in three hospitals, both prospectively and retrospectively. Collection data consisted of patient information, job characteristics and duration of sick leave during the month before and the month after control. The valuation of sick leave used the friction cost method. RESULTS: Among the 306 patients included, 292 (95%) completed the entire questionnaire. The mean age was 46.7 years. Among the 194 active patients, patients treated with rhTSH, when compared with patients treated by withdrawal, were less likely to require sick leave (11 vs 33%; P=0.001). The mean duration of sick leave was shorter (3.1 vs 11.2 days; P=0.002) and indirect costs due to absenteeism accounted for 454 Euro +/- 1673 vs 1537 Euro +/- 2899 for withdrawal stimulation. CONCLUSION: For active patients, rhTSH treatment reduced the length and the cost of sick leave by 8.1 days and 1083 Euro per control respectively, when compared with withdrawal treatment.