ICI Rechallenge Shows Moderate Efficacy for Treatment of mRCC

A multicenter, retrospective cohort study on immune checkpoint inhibitor (ICI) rechallenge for treating patients with metastatic renal cell carcinoma (mRCC) found the method to be moderately efficacious (JAMA Oncol. 2020 Oct 1;6(10):1606-1610.).

“Several immune checkpoint inhibitors (ICIs) are approved for use in patients with metastatic renal cell carcinoma (mRCC), but the efficacy and safety of ICI rechallenge in mRCC is unknown,” wrote Praful Ravi, MBBChir, Dana-Farber Cancer Institute, Boston, Massachusetts, and colleagues.

The study included 69 patients (50 men, 19 women) from 9 institutions across the US, all of whom have mRCC and received at least two separate lines of ICI (ICI-1, ICI-2) between January 2012 and December 2019.

In at least two separate lines of therapy for mRCC, patients received an ICI (anticytotoxic T-lymphocyte-associated protein 4, anti-programmed cell death protein 1, or anti-programmed cell death ligand 1), alone or in combination with other therapies. The most common therapies received at ICI-1 were single-agent ICI (n = 27 [39%]) or ICI in combination with targeted therapy (n = 29 [42%]). At ICI-2, the most common therapies were single-agent ICI (n = 26 [38%]) or dual ICI (n = 22 [32%]).

The overall response rate (ORR) at ICI-1 was 37%, while ICI-2 had an ORR of 23%. Researchers also found that patients who previously responded to ICI-1 (7 of 24 [29%]) had a higher likelihood of responding to ICI-2. However, responses at ICI-2 were still seen in those who had progressive disease following ICI-1 (3 of 14 [21%]) as well as in those who received single-agent ICI at ICI-2 (7 of 23 [30%]).

Immune-related adverse events grade 3 or higher were seen in 18 patients (26%) and 11 patients (16%) at ICI-1 and ICI-2, respectively. Furthermore, a majority of patients discontinued ICI-1 due to disease progression (n = 50 [72%]) or toxic effects (n = 16 [23%]). No treatment-related deaths were reported.

“The findings of this multicenter cohort study suggest that ICI rechallenge in patients with mRCC may be safe and reasonably efficacious, with an overall response rate of 23%. Data from prospective studies are needed to validate these findings and determine the role of sequential ICI regimens in treatment of mRCC,” concluded Ravi et al.—Alexandra Graziano