Discontinuation of Immune-oncology Combinations due to Immune-related Adverse Events in Patients With Advanced Renal Cancers

Background/aim: Patients with advanced renal cell carcinoma (aRCC) treated with immune-oncology (IO) drugs may need to discontinue the treatment when severe immune-related adverse events (irAE) occur; however, the impact of discontinuation on survival remains unknown.

Patients and methods: This is a retrospective multicenter analysis using a database of 183 aRCC patients treated with first-line IO drugs combination. The patients were divided into two groups according to the necessity of discontinuation due to irAEs. The primary endpoint was overall survival (OS). Cox proportional hazard models determined the predictive factors on OS.

Results: Among a total of 135 patients who experienced irAE, 38 patients had to discontinue and 52 continued the treatment while treating irAE. When compared to patients who were able to continue treatment, discontinuation was associated with significantly higher rates of IO-IO doublet use, severe irAE (grade ≥3), steroid use, and the occurrence of immune-related pneumonitis (p=0.03, p<0.001, p<0.001, and p=0.02, respectively). The objective response rates were comparable between the two groups (discontinuation 55.6% vs. no discontinuation 56.0%, p=0.7). On univariate analysis, patients who discontinued had a significantly worse OS when compared to those who continued treatment (p=0.02). On the contrary, on multivariate analysis treatment discontinuation was not associated with poor OS (HR=1.1, p=0.9).

Conclusion: Treatment discontinuation due to irAE was not associated with poor prognosis in aRCC patients treated with ICI-based combination therapy. Treatment discontinuation may be a reasonable treatment option for well-selected patients, specifically for those who experienced good treatment responses.