Outcomes of PD-1/PD-L1 responders who discontinue therapy for immune-related adverse events (irAEs): Results of a cohort of patients (pts) with metastatic renal cell carcinoma (mRCC).

Abstract

467 Background: Nivolumab, a monoclonal antibody against PD-1, has been shown to improve survival for pts with mRCC. The current standard of care is to administer treatment on a continuous basis until progression or toxicity. Outcomes of pts who experience a response to treatment and then discontinue therapy for irAEs have not been fully characterized. The purpose of this analysis was to evaluate outcomes of responders to PD-1/PD-L1 targeted therapy (TT) who discontinue treatment for irAEs. Methods: We identified pts with mRCC having experienced a response to PD-1/PD-L1 TT, which was subsequently discontinued for an irAE. Clinical characteristics, response, and survival data were collected. Results: We identified 9 mRCC pts who were treated with a PD-1/PD-L1 inhibitor, experienced a response to therapy, and subsequently discontinued treatment for an irAE. 8 had clear cell histology and 1 had translocation RCC. 7 pts were treatment naive. 2 pts had International mRCC Database Consortium favorable risk, 4 intermediate risk, and 3 poor risk disease. 44% (n = 4) of pts received PD-1/PD-L1 monotherapy and the overall median duration of therapy was 5 months (mos) (range 4-15). There was 1 complete response, 7 partial responses, and 1 stable disease (17% shrinkage). Treatment was discontinued for the following irAEs: arthritis, uveitis, arthropathy, hypophysitis, myositis, blepharitis, hepatitis, rash, pericarditis, and amylase and lipase elevations. After PD-1/PD-L1 treatment discontinuation, 4 (44%) pts remained progression free with a median time off therapy of 20 mos (range 10-44) and median time on therapy of 9 mos (range 4-15). 5 (56%) pts progressed within 6 mos (range 2-6) of treatment discontinuation and median time on therapy was 4 mos (range 3-10). Conclusions: We demonstrate that some pts can have persistent clinical benefit after discontinuation of PD-1/PD-L1 TT for irAEs. Larger studies are warranted to evaluate the need for continuous drug dosing in all pts, identify pts in which continuous dosing is not required, and evaluate long-term outcomes in this population.