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DOI: 10.1158/2326-6066.cir-17-0220
OpenAccess: Closed
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Durable Clinical Benefit in Metastatic Renal Cell Carcinoma Patients Who Discontinue PD-1/PD-L1 Therapy for Immune-Related Adverse Events

Dylan J. Martini,Lana Hamieh,Rana R. McKay,Lauren C. Harshman,Raphael Brandão,Craig Norton,John A. Steinharter,Katherine M. Krajewski,Xīn Gào,Fábio Augusto Barros Schütz,Bradley A. McGregor,Dominick Bossé,Aly-Khan A. Lalani,Guillermo Velasco,M. Dror Michaelson,David F. McDermott,Toni K. Choueiri

Medicine
Pneumonitis
Renal cell carcinoma
2018
Abstract The current standard of care for treatment of metastatic renal cell carcinoma (mRCC) patients is PD-1/PD-L1 inhibitors until progression or toxicity. Here, we characterize the clinical outcomes for 19 mRCC patients who experienced an initial clinical response (any degree of tumor shrinkage), but after immune-related adverse events (irAE) discontinued all systemic therapy. Clinical baseline characteristics, outcomes, and survival data were collected. The primary endpoint was time to progression from the date of treatment cessation (TTP). Most patients had clear cell histology and received anti–PD–1/PD-L1 therapy as second-line or later treatment. Median time on PD-1/PD-L1 therapy was 5.5 months (range, 0.7–46.5) and median TTP was 18.4 months (95% CI, 4.7–54.3) per Kaplan–Meier estimation. The irAEs included arthropathies, ophthalmopathies, myositis, pneumonitis, and diarrhea. We demonstrate that 68.4% of patients (n = 13) experienced durable clinical benefit off treatment (TTP of at least 6 months), with 36% (n = 7) of patients remaining off subsequent treatment for over a year after their last dose of anti–PD-1/PD-L1. Three patients with tumor growth found in a follow-up visit, underwent subsequent surgical intervention, and remain off systemic treatment. Nine patients (47.4%) have ongoing irAEs. Our results show that patients who benefitted clinically from anti–PD-1/PD-L1 therapy can experience sustained beneficial responses, not needing further therapies after the initial discontinuation of treatment due to irAEs. Investigation of biomarkers indicating sustained benefit to checkpoint blockers are needed. Cancer Immunol Res; 6(4); 402–8. ©2018 AACR.
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    Durable Clinical Benefit in Metastatic Renal Cell Carcinoma Patients Who Discontinue PD-1/PD-L1 Therapy for Immune-Related Adverse Events” is a paper by Dylan J. Martini Lana Hamieh Rana R. McKay Lauren C. Harshman Raphael Brandão Craig Norton John A. Steinharter Katherine M. Krajewski Xīn Gào Fábio Augusto Barros Schütz Bradley A. McGregor Dominick Bossé Aly-Khan A. Lalani Guillermo Velasco M. Dror Michaelson David F. McDermott Toni K. Choueiri published in 2018. It has an Open Access status of “closed”. You can read and download a PDF Full Text of this paper here.