Association Between Regorafenib-Induced Proteinuria and Survival in Patients with Metastatic Colorectal Cancer: A Single-Center Retrospective Study

In patients with metastatic colorectal cancer (mCRC), the risk factors of regorafenib (REG)-induced proteinuria and its clinical impact are poorly understood. Therefore, we retrospectively investigated the onset and characteristics of proteinuria, the effect of the interval between the final bevacizumab (BEV) administration and the initial REG administration on the onset of proteinuria, and proteinuria’s impact on overall survival (OS) in patients with mCRC who received sequential administration of BEV to REG. Among the 31 eligible patients, the incidence of grades 1, 2, and 3 proteinuria based on dipstick urinalysis was 25.8％, 58.1％, and 16.1％, respectively. The median (range) time to improvement in urinary protein ≤2+ in patients with urinary protein ≥3+ was 14 (7 – 14) days in the REG withdrawal/reduction group (n = 4) and 17 (7 – 33) days in the discontinuation group (n = 10). The incidence of urinary protein ≥2+ tended to decrease among patients with a longer interval between BEV and REG (P = 0.15). The median OS was significantly longer in patients with urinary protein ≥3+ than in those with urinary protein ≤2+ (365 days vs 153 days, P = 0.03). In patients with mCRC, REG-induced proteinuria can positively impact OS, and its occurrence can be predicted by the interval between the final BEV and initial REG. Given that severe proteinuria can improve following REG interruption, treatment continuation should be carefully evaluated.