Nivolumab Can Still Benefit RCC Patients Who Stop Due to Immune-Related Toxicity
A small study found that patients with metastatic renal cell carcinoma (mRCC) who discontinue nivolumab due to immune-related adverse events can continue to derive benefit even after cessation of therapy.
A small study found that patients with metastatic renal cell carcinoma (mRCC) who discontinue nivolumab due to immune-related adverse events (irAEs) can continue to derive benefit even after cessation of therapy.
“Nivolumab has been shown to improve overall survival and overall response rates in patients with VEGF-refractory RCC,” said Dylan Martini, of the Dana-Farber Cancer Institute in Boston, who presented the new study at the 15th International Kidney Cancer Symposium (IKCS), held November 4–5 in Miami, Florida. The current standard, he added, is to administer nivolumab on a continuous basis until disease progression or until intolerable toxicity. In one large trial, 8% of patients discontinued nivolumab due to irAEs. “How long can they stay off treatment for?” Martini asked.
The study included nine patients across all IMDC risk groups from Dana-Farber’s patient database. Seven of nine patients had clear cell histology.
Seven of the patients achieved a partial response as their best response to therapy, and there was one complete response and one patient with stable disease; the median time off therapy was 6 months. Five patients were found to be “durable responders,” meaning they remained in remission after stopping nivolumab therapy due to an irAE. Among those patients, the time off therapy ranged from 6 months up to 44 months. Two durable responders were on nivolumab for only 4 months and 5 months, respectively, and then were able to maintain their response for 19 and 10 months, respectively.
Two patients were “eventual progressors,” who were progression-free for an interval following nivolumab cessation before progressing. The time off therapy for these patients was 6 and 5 months, respectively. Two other patients were “immediate progressors,” and progressed within 2 months of stopping the therapy.
Martini said larger studies are needed to better understand the persistence of clinical benefit in RCC patients who stop immunotherapy agents for irAEs.
In a separate talk at IKCS, Neeraj Agarwal, MD, of the Huntsman Cancer Institute in Salt Lake City, Utah, said that clinical trials often have suboptimal reporting of AEs and irAEs in particular. He noted that though PD-1/PD-L1 inhibitors like nivolumab may have irAEs that are quite rare, the real-world magnitude of the AEs is expected to be much higher because of the likely ubiquity of the agents’ use.
