In clinical trials, laboratory values are assessed with high frequency. This can be stressful for patients, resource intensive, and difficult to implement, for example in office-based settings. In the prospective, multicentre phase 2 TITAN-RCC trial (NCT02917772), we investigated how many relevant changes in laboratory values would have been missed if laboratory values had been assessed less frequently. Patients with metastatic renal cell carcinoma (n = 207) received a response-based approach with nivolumab and nivolumab+ipilimumab boosts for non-response. We simulated that laboratory values were obtained before every second dose instead of every dose of the study drug(s). We assessed elevated leukocyte counts, alanine aminotransferase, aspartate aminotransferase, bilirubin, creatinine, amylase, lipase, and thyroid-stimulating hormone. Dose delay and discontinuation criteria were defined according to the study protocol. With the reduced frequency of laboratory analyses, dose delay criteria were rarely missed: in a maximum of <0.1% (3/4382) of assessments (1% [2/207] of patients) during nivolumab monotherapy and in a maximum of 0.2% (1/465) of assessments (1% [1/132] of patients) during nivolumab+ipilimumab boosts. An exception was lipase-related dose delay which would have been missed in 0.6% (25/4204) of assessments (7% [15/207] of patients) during nivolumab monotherapy and in 0.8% (4/480) of assessments (3% [4/134] of patients) during nivolumab+ipilimumab boosts, but would have required the presence of symptoms. Discontinuation criteria would have only been missed for amylase (<0.1% [1/3965] of assessments [0.5% (1/207) of patients] during nivolumab monotherapy, none during nivolumab+ipilimumab boosts) and lipase (0.1% [5/4204] of assessments [2% (4/207) of patients] during nivolumab monotherapy; 0.2% [1/480] of assessments [0.7% (1/134) of patients] during nivolumab+ipilimumab boosts). However, only symptomatic patients would have had to discontinue treatment due to amylase or lipase laboratory values. In conclusion, a reduced frequency of laboratory testing appears to be acceptable in asymptomatic patients with metastatic renal cell carcinoma treated with nivolumab or nivolumab+ipilimumab.
在临床试验中，实验室指标的评估频率通常较高。这可能给患者带来压力、消耗大量资源且实施困难，例如在门诊环境中。在前瞻性、多中心II期TITAN-RCC试验（NCT02917772）中，我们研究了若降低实验室指标评估频率，将遗漏多少具有临床意义的指标变化。转移性肾细胞癌患者（n=207）接受基于应答的治疗方案：使用纳武利尤单抗，对无应答者加用纳武利尤单抗+伊匹木单抗强化治疗。我们模拟将实验室指标检测频率从每次给药前调整为每两次给药前检测一次。评估指标包括白细胞计数、丙氨酸氨基转移酶、天冬氨酸氨基转移酶、胆红素、肌酐、淀粉酶、脂肪酶和促甲状腺激素的升高情况。剂量延迟和停药标准依据研究方案设定。降低检测频率后，剂量延迟标准极少被遗漏：纳武利尤单抗单药治疗期间最多有<0.1%（3/4382）的检测（涉及1%[2/207]的患者）被遗漏；纳武利尤单抗+伊匹木单抗强化治疗期间最多有0.2%（1/465）的检测（涉及1%[1/132]的患者）被遗漏。脂肪酶相关剂量延迟是例外情况：纳武利尤单抗单药治疗期间0.6%（25/4204）的检测（涉及7%[15/207]的患者）可能被遗漏；纳武利尤单抗+伊匹木单抗强化治疗期间0.8%（4/480）的检测（涉及3%[4/134]的患者）可能被遗漏，但此类情况需伴有临床症状才需调整剂量。停药标准仅可能遗漏淀粉酶（纳武利尤单抗单药治疗期间<0.1%[1/3965]的检测涉及0.5%[1/207]的患者，联合治疗期间无遗漏）和脂肪酶（单药治疗期间0.1%[5/4204]的检测涉及2%[4/207]的患者；联合治疗期间0.2%[1/480]的检测涉及0.7%[1/134]的患者）。但需注意，仅出现临床症状的患者才需要因淀粉酶或脂肪酶异常而终止治疗。结论：对于接受纳武利尤单抗或纳武利尤单抗+伊匹木单抗治疗的转移性肾细胞癌无症状患者，降低实验室检测频率似乎是可接受的。
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