Reasonability of Frequent Laboratory Analyses during Therapy with Nivolumab and Nivolumab+Ipilimumab in Patients with Advanced or Metastatic Renal Cell Carcinoma during the Phase 2 Clinical Trial TITAN-RCC.

Simple Summary: In this work, we evaluated the need for frequent laboratory assessments in patients with metastatic renal cell carcinoma treated with nivolumab and nivolumab+ipilimumab during the TITAN-RCC clinical trial. We analysed how often reached criteria for dose delay or permanent discontinuation of therapy would have been missed if the frequency of laboratory testing had been reduced, in order to avoid over-sampling patients and to optimise clinical workflow and staffing. Our study showed that if the frequency of laboratory tests had been reduced, reached dose delay criteria would hardly have been missed. This would have affected up to 1% (2/207) of patients. An exception was dose delay due to the elevation of lipase blood levels which would have been missed in up to 7% (15/207) of patients. However, these patients presented with symptoms and would have been identified based thereupon. Discontinuation criteria would have only been overlooked for lipase (2% [4/207] of patients) and amylase (0.5% [1/207] of patients). Again, these patients would have been identified, since only symptomatic patients would have needed to discontinue treatment due to amylase or lipase laboratory values. In conclusion, in asymptomatic patients in our setting, laboratory analyses do not seem to be necessary before every treatment application. 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. [ABSTRACT FROM AUTHOR]