Donia Marco, Kimper-Karl Marie Louise, Høyer Katrine Lundby, Bastholt Lars, Schmidt Henrik, Svane Inge Marie
Center for Cancer Immune Therapy, Department of Hematology, Herlev, Denmark; Department of Oncology, Copenhagen University Hospital, Herlev, Denmark.
Department of Oncology, Odense University Hospital, Odense, Denmark.
Eur J Cancer. 2017 Mar;74:89-95. doi: 10.1016/j.ejca.2016.12.017. Epub 2017 Feb 12.
Recent randomised phase III trials have led to the approval of several immune checkpoint inhibitors for unresectable or metastatic melanoma (MM). These trials all employed strict patient selection criteria, and it is currently unknown how large proportion of 'real-world' patients diagnosed with MM is not represented in these trials.
The Danish MM Database contains data on the entire, unselected population of MM within a nationwide geographical area. A total of 276 unselected cases of MM (ocular melanoma excluded), referred for first oncological evaluation in 2014, were included in the analysis. Seven pre-defined eligibility criteria, all used to select patients for enrolment in five recent randomised phase III immunotherapy trials, were analysed.
Fifty-five percent of the total population with MM did not meet one or more eligibility criteria ('not eligible' group) at first evaluation. PS ≥ 2 or active/untreated known brain metastases accounted alone for 74% of non-eligibility cases. Median overall survival in the 'not eligible' group was 5.43 months versus 18.3 months for the eligible (p < 0.0001, hazard ratio (HR) 2.44), reflected by significantly worse baseline prognostic features. However, patients treated with immunotherapy had similar survival outcomes regardless of eligibility.
Over half of the patients evaluated for systemic treatment of MM are not represented in phase III registration immunotherapy trials. The data reveal a huge knowledge gap regarding the usefulness of new immunotherapies in the 'real-world' patient population, and urge additional testing of known regimens in selected poor prognosis cohorts.
近期的随机III期试验已促使几种免疫检查点抑制剂获批用于不可切除或转移性黑色素瘤（MM）。这些试验均采用了严格的患者选择标准，目前尚不清楚在这些试验中未纳入的被诊断为MM的“真实世界”患者占多大比例。
丹麦MM数据库包含全国地理区域内全部未经过选择的MM患者数据。2014年被转诊进行首次肿瘤学评估的总共276例未经过选择的MM病例（不包括眼黑色素瘤）被纳入分析。分析了七个预先定义的入选标准，这些标准均用于选择患者参加最近的五项随机III期免疫治疗试验。
在首次评估时，MM患者总数的55%不符合一项或多项入选标准（“不符合标准”组）。仅PS≥2或有活动性/未经治疗的已知脑转移就占不符合标准病例的74%。“不符合标准”组的中位总生存期为5.43个月，而符合标准组为18.3个月（p<0.0001，风险比（HR）2.44），这反映出基线预后特征明显更差。然而，接受免疫治疗的患者无论是否符合标准，生存结果相似。
在III期注册免疫治疗试验中未纳入超过一半接受MM全身治疗评估的患者。数据揭示了关于新免疫疗法在“真实世界”患者群体中的有用性方面存在巨大的知识空白，并敦促在选定的预后不良队列中对已知方案进行额外测试。
