The bump in 5-year survival rates for people with advanced or metastatic renal cell carcinoma (RCC) can be traced to the development of oral targeted agents, including tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors. But there’s a dearth of research about possible adverse effects linked to those agents in patients with renal impairment or end-stage renal disease (ESRD). However, because many of those agents are renally eliminated, their use in treating RCC may increase the risk of adverse events.
A team of researchers set out to learn more about how well patients with metastatic RCC and renal impairment or ESRD tolerate those oral targeted therapies. Their findings were published in the Journal of Hematology Oncology Practice.
“The purpose of our study was to assess the tolerability, safety, and efficacy of FDA-approved oral targeted agents for metastatic RCC in patients with moderate-to-severe renal impairment or with ESRD who are undergoing dialysis, to provide guidance for clinicians when managing patients with metastatic RCC,” the researchers explained.
The study included 55 patients, all of whom had experienced at least 1 adverse event from treatment with an oral targeted therapy, and received 74 treatment episodes. Nearly 73% of the patients experienced a grade 1 or 2 adverse event, and 67.3% experienced a grade 3 or 4 adverse event. Fatigue was the most common adverse event, followed by hypertension, nausea, appetite suppression, anorexia, diarrhea, weight loss, and dysgeusia. The researchers noted that adverse events led to a dose reduction in 33 (44.6%) treatment episodes, treatment interruption in 42 (56.8%) treatment episodes, and discontinuation in 42 (56.8%) treatment episodes.
“The incidence of adverse events in patients with metastatic RCC receiving an oral targeted agent remains prominent on those with renal impairments,” the researchers observed. The overall survival outcomes were similar to previous studies, and useful new information about decreased safety in the use of cabozantinib in patients with RCC and renal impairment was uncovered.
“These results raise questions about the safety of oral targeted agents in patients with metastatic RCC and renal impairment,” the researchers cautioned. “[B]ut these drugs may still be considered for this patient population if increased monitoring is implemented.”
The study limitations included that this was a retrospective study with only 1 independent reviewer for all adverse events and disease progression determinations. The number of patients receiving each oral targeted therapy varied, and the study had no direct control cohort.
However, the study does add to the growing body of knowledge regarding the use of oral targeted agents in patients with metastatic RCC, including those with renal impairment and ESRD.
McKernan J, Schmidt L, Rhoades M. Tolerance of oral targeted therapies in patients with metastatic renal-cell carcinoma and renal impairment. J Hematol Oncol Pharm. 2021;11(5):270-276.