Nivolumab Is a Cost-Effective Second-Line Treatment for Metastatic Renal-Cell Carcinoma

Introduction

The introduction of active new agents, such as small molecules and checkpoint inhibitors, for the treatment of metastatic renal-cell cancer (mRCC) is associated with a relevant increase in costs, and it is therefore important to strike a balance between the costs of treatment and the added value represented by the improvement of the clinical parameters of interest such as progression-free survival (PFS) and overall survival (OS).

Five years of EMA-approved systemic cancer therapies for solid tumours—a comparison of two thresholds for meaningful clinical benefit

ObjectiveSeveral societies have proposed frameworks to evaluate the benefit of oncology drugs; one prominent tool is the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). Our objectives were to investigate the extent of European Medicines Agency (EMA)-approved cancer drugs that meet the threshold for ‘meaningful clinical benefit’ (MCB), defined by the framework, and determine the change in the distribution of grades when an adapted version that addresses the scale's limitations is applied.MethodsWe identified cancer drugs approved by the EMA (2011–2016). We previously proposed adaptations to the ESMO-MCBS addressing its main limitations, including the use of the lower limit of the 95% confidence interval in assessing the hazard ratio. To assess the MCB, both the original and adapted ESMO-MCBS were applied to the respective approval studies.ResultsIn total, we identified 70 approval studies for 38 solid cancer drugs. 21% of therapies met the MCB threshold by the original ESMO-MCBS criteria. In contrast, only 11% of therapies met the threshold for MCB when the adapted ESMO-MCBS was applied. Thus 89% and 79% of therapies did not meet the MCB threshold in the adapted and original ESMO-MCBS, respectively.ConclusionsIn most of the cancer drugs, the MCB threshold is not met at the time of approval when measured using both ESMO-MCBS scales. Since approval status does not translate into a MCB, stakeholders and decision makers should focus on the benefit/risk ratio of anticancer drugs to assure an appropriate allocation of resources in health care systems.     

抗癌药物评定标准：统计学差异还是临床获益？

2012—2016年PubMed上发表的肿瘤相关性RCT研究超过10 000项,较2000—2004年的发表量翻了1倍。如何评价如此庞杂的研究结果,将这些成果应用于临床决策,是一个值得思考的问题。抗癌药物价值的评判不仅包括其对患者生存的影响,还包括不良反应、经济因素等。因此,临床亟待新的标准全面评判抗肿瘤药物的临床获益。近期,欧洲临床肿瘤协会(the European Society for Medical Oncology,ESMO)与美国临床肿瘤学会(the American Society of Clinical Oncology)相继出台了评价肿瘤患者临床获益的标准,即ESMO-MCBS(Magnitude of Clinical Benefit Scale)、ASCO-VF(Value Framework)。采用以上标准后显示,在评价临床研究结果时,单凭统计学差异是不够的。抗癌药物临床研究的评价应以统计学差异为基础,以临床获益为目标,以期切实改善肿瘤患者的生存。     

Randomized controlled trial in gastric or gastroesophageal junction adenocarcinoma undergoing systemic therapy over two decades

IntroductionThe number of randomized controlled trials (RCTs) investigating the systemic treatment of gastric or gastroesophageal junction adenocarcinoma (GA-RCTs) is increasing. We aimed to describe the characteristics and evaluate the clinical benefit of GA-RCTs over the past 20 years.Materials and methodsWe searched for RCTs of systemic treatment in GA published in eight major journals between 2001 and 2020 in PubMed. From the included studies, the characteristics and results of GA-RCTs were extracted. Clinical benefit was assessed using the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS).ResultsAbout 93 RCTs with 38365 patients were included. Seventy-one (76.3%) studies received external funding, with an increase from 27.3% (2001–2005) to 94.1% (2016–2020). RCTs on targeted therapy and/or immunotherapy have also increased over time, but only 14 (41.2%) were restricted to specific biomarkers. Forty-four (47.3%) studies met their primary endpoint (defined as positive RCTs), but median overall survival has not improved over time. Moreover, only 16 (36.4%) studies met the ESMO-MCBS threshold. RCTs whose study design and results met the ESMO-MCBS thresholds has not increased over time (p = 0.827 and p = 0.733, respectively).ConclusionsGA-RCTs are increasingly focused on targeted therapy and/or immunotherapy, and are more likely to receive external funding. However, the effect size has not shown significant improvement in the past 20 years. Only a few RCTs with positive results met ESMO thresholds. Future RCTs should prioritize the clinical benefits and provide direct evidence to optimize and reform GA treatment practices.