MS 20.02 Value-Based Judgment in Advanced NSCLC: The European Perspective

Abstract

Therapy of lung cancer depends on many factors including tumor-related factors, patient parameters and treatment-related factors. Tumor-related factors are histological subtype, molecular characteristics and stage as well as growth of tumors. Patient-related factors include age, life expectancy, gender, performance status, organ functions, co-morbidity, functional status, geriatric syndromes and patient preference. Drug-related parameters include convenience of administration, side effects of drugs, and polypharmacy. Costs, cost effectiveness and value-based judgements are also of major importance. Value-based judgements of anticancer therapies are based on the magnitude of the clinical benefit balanced against their costs.1 These judgements are gaining increasing importance because of the increasing costs of modern anticancer treatments including novel anticancer drugs. The benefit of treatments focus on living longer and living better. The evidence of the magnitude of the treatment benefit is derived from clinical trials such as phase 3 trials or from meta-analyses of randomized trials. Important outcome parameters focus on the impact of the treatments on overall survival, progression-free survival, response rates and symptom relief. Parameters for living longer are improved overall survival and/or improved surrogate of overall survival such as disease-free survival in the adjuvant setting or progression-free survival. With regard to living better, important parameters are improved quality of life, improved surrogate of quality of life, and reduced toxicity. The incremental cost-effectiveness ratio (ICER) is often used to evaluate the value of a new anticancer drug.2,3 ICER refers to the costs per life year gained or costs per quality-adjusted life year gained. A drug is considered cost-effective if its ICER is below a certain threshold which depends on the country and may range from about 20.000 to 50.000 Euros or even higher. Several scientific and professional societies including ESMO have developed scales to determine the clinical benefit of systemic treatments in patients with cancer. The ESMO - Magnitude of Clinical Benefit Scale (ESMO-MCBS) is a standardized, generic, validated tool to assess the magnitude of clinical benefit that can be expected form anticancer therapies.4,5 This tool is dynamic and has been planned to be revised in regular intervals.4 Separate tools have been developed for the adjuvant and the palliative settings. For assessment of survival data, hazard ratios and median survival times are considered. Based on simulation data, the lower limit of the 95% confidence interval of the hazard ratios have been recommended for use.4 Form 1 of the ESMO-MCBS is used for adjuvant or neoadjuvant therapies and for localized or metastatic disease treated with curative intent.4 The grades are A, B and C, with grades A and B representing high levels of clinical benefit.4 Grade A refers to >5% improvement in survival or improvement in disease-free survival alone with a HR<0.65 in studies without mature survival data. Grade B refers to ≥3% but ≤5% improvement in survival or improvement in disease-free survival alone with hazard ratios <0.65-0.8 without mature survival data. In addition, non-inferior survival or disease-free survival with reduced treatment toxicity or improved quality of life, or non-inferior survival with reduced treatment costs are also graded as B. Grade C refers to <3% improvement of survival or improvement in disease-free survival alone with hazard ratios >0.8 in studies without mature survival data. Form 2 of the ESMO-MCBS is used for therapies without curative intent.4 The grades range from 1 to 5, with grades 4 and 5 representing high levels of proven clinical benefit.4 Form 2 is more complex and includes forms 2a, 2b and 2c. Form 2a is for therapies that are not likely to be curative and have overall survival as primary endpoint. Form 2b is for therapies that are not likely to be curative and have progression-free survival as primary endpoint. Form 2c is for therapies that are not likely to be curative and have primary endpoints other than overall survival or progression-free survival. The preliminary magnitude of clinical benefit is based on the efficacy of the treatment and is then adjusted according to quality of life and grade 3-4 toxicities. The preliminary score is upgraded by 1 if the treatment resulted in improved quality of life and/or less grade 3-4 toxicities. The ESMO-MCBS is planned for comparative analyses of different treatments.4,5 The value of treatments of lung cancer measured according to the ESMO-MCBS in a single institution has recently been published (6). In summary, the evaluation of the clinical benefit of anticancer therapies in patients with lung cancer is a complex and rapidly moving area. It is based on the evidence from clinical trials, cost effectiveness analyses and, more recently, also valued-based judgements. The latter tools are dynamic and balance magnitudes of the benefits against the costs of specific treatments. Despite all these measures, clinically experienced doctors working in close co-operation with informed patients and their relatives are crucial for optimal treatment decisions in patients with lung cancer.