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Adverse Events and Outcomes in Patients Receiving Anti–PD-1/PD-L1 Antibody Treatment for Advanced Urothelial Cancer

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Key Points

  • Responders were more likely to have treatment-related adverse events of special interest or immune-mediated adverse events than nonresponders.
  • Systemic corticosteroid use did not appear to affect duration of response.   

In an analysis reported in the Journal of Clinical Oncology, Maher et al found that treatment-related adverse events of special interest and immune-mediated adverse events were more common among patients with advanced urothelial cancer with vs without response to anti–programmed cell death protein 1 or ligand 1 (anti–PD-1/PD-L1) antibody treatment.

Study Details

The analysis involved data from 1,747 patients with metastatic or locally advanced urothelial cancer from 7 clinical trials that led to approval of an anti–PD-1/PD-L1 antibody. Of these, five trials enrolled patients who had received prior platinum-based therapy and two enrolled patients who were cisplatin-ineligible; six of the trials were single-arm studies. Data sets were searched for adverse events of special interest, drug-related adverse events of special interest, immune-mediated adverse events, and drug-related immune-mediated adverse events, with relationship to study drug being determined by trial investigators. Immune-mediated adverse events were defined as adverse events of special interest treated with topical or systemic corticosteroids. Responses were confirmed responses using RECIST v1.1 criteria.

Association With Outcomes

Overall, a treatment-related adverse event of special interest was reported in 64% of responding patients and in 34% of patients who did not respond to anti–PD-1/PD-L1 antibody treatment. A treatment-related immune-mediated adverse event was found in 28% of patients who responded and 12% of patients who did not respond to treatment.  In analysis adjusted for baseline covariates, patients developing a treatment-related adverse event of special interest (hazard ratio [HR] = 0.45, 95% confidence interval [CI] = 0.39–0.53) or a treatment-related immune-mediated adverse event (HR = 0.53, 95% CI = 0.43–0.66) had improved overall survival compared with patients with no treatment-related adverse events of special interest or no treatment-related immune-mediated adverse event. Treatment-related adverse events of special interest occurred prior to documentation of response in 57% of responders; the most common treated-related adverse events of special interest seen before response were pruritus, rash, and thyroid disease. The association between response and development of related adverse events of special interest/ immune-mediated adverse events was maintained in multivariable analysis adjusting for duration of exposure to study drug. Responding patients who did vs did not receive systemic corticosteroids for any reason, including immune-mediated adverse events, had similar durations of response (HR = 1.09, 95% CI = 0.70-1.69).

The investigators concluded, “Patients who responded to treatment with an [anti–PD-1/PD-L1] antibody were more likely to report a related adverse event of special interest or related immune-mediated adverse event. This relationship did not seem to be due to the increased duration of exposure in responding patients. Systemic corticosteroid use did not appear to affect the duration of response.”

V. Ellen Maher, MD, of the U.S. Food and Drug Administration, is the corresponding author for the Journal of Clinical Oncology article. For full disclosures of the study authors, visit jco.ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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