Immunotherapy Rechallenge 'Reasonably' Effective in Metastatic Kidney Cancer

By Megan Brooks

June 08, 2020

NEW YORK (Reuters Health) - Immunotherapy rechallenge in patients with metastatic renal-cell carcinoma (mRCC) appears to be safe and "reasonably efficacious," according to what is believed to be the largest study reporting on outcomes of immunotherapy rechallenge in this patient group.

Dr. Praful Ravi of Dana-Farber Cancer Institute in Boston reported the results May 29 during the American Society of Clinical Oncology (ASCO) 2020 virtual annual meeting, with simultaneous publication in JAMA Oncology.

Several immune-checkpoint inhibitors (ICIs) - nivolumab, ipilimumab, avelumab and pembrolizumab - are approved and widely used (alone or in combination) in patients with mRCC.

"Use of these agents has significantly improved outcomes. The median survival now approaches nearly four years in patients treated with frontline ipilimumab/nivolumab," Dr. Ravi said during his presentation.

"However, many, if not most patients treated with immunotherapy for kidney cancer ultimately progress. Oncologists may therefore attempt rechallenge with a checkpoint inhibitor," but the efficacy and safety of ICI rechallenge in mRCC is unknown, he added.

To investigate, a multicenter team of clinicians did a retrospective cohort study of 69 consecutive patients with mRCC from nine institutions in the U.S. who received at least two separate lines of ICI (ICI-1, ICI-2) between 2012 and 2019. The median age at diagnosis of mRCC was 61 years; nearly 90% had clear-cell histology.

The most common therapies received at ICI-1 were single-agent ICI (39%) or ICI in combination with targeted therapy (42%), while at ICI-2, the most common therapies were single-agent ICI (38%) or dual ICI (32%).

The most common reason for stopping ICI-1 was disease progression (72%), although about one in five stopped for toxic effects (23%).

Overall, among 68 evaluable patients at ICI-1, the response rate was 37%. Among 64 evaluable patients at ICI-2, the response rate was lower (23%).

Patients who responded at ICI-1 had a higher chance of responding at ICI-2 compared with those who had either stable disease or disease progression at ICI-1. The response at ICI-2 was higher in those who had stopped ICI-1 for toxicity, as opposed to those who had stopped due to disease progression, Dr. Ravi reported.

Nearly half of patients had some form of immune-related adverse event at ICI-2, Dr. Ravi said. Fewer patients suffered grade-3-or-higher immune-related adverse events at ICI-2 than ICI-1 (16% vs. 26%). There were no treatment-related deaths.

Summing up, Dr. Ravi said this study suggests that the response to ICI re-challenge is "around 20%, which is a reasonable number and not too dissimilar to that seen with single-agent avelumab in the second-line post-tyrosine-kinase setting. Responses were seen even with single-agent ICI at ICI-2, as well as in those who had not responded to prior line of ICI. Finally, ICI re-challenge appeared relatively safe. Going forward, we await data from prospective trials to see whether sequential use of immunotherapy has a role to play in kidney cancer."

This study had no specific funding, and Dr. Ravi has no relevant disclosures.

SOURCE: JAMA Oncology, online May 29, 2020.