FDA Updates Restrictions for Pembrolizumab, Atezolizumab in Urothelial Carcinoma

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Atezolizumab and pembrolizumab were FDA-approved for the treatment of urothelial carcinoma in 2016 and 2017, respectively.
Atezolizumab and pembrolizumab were FDA-approved for the treatment of urothelial carcinoma in 2016 and 2017, respectively.

The US Food and Drug Administration (FDA) has recommended restricting the use of pembrolizumab or atezolizumab monotherapy among previously untreated patients with advanced or metastatic urothelial carcinoma not eligible for cisplatin-based chemotherapy, according to a press release.1

Atezolizumab and pembrolizumab — immunotherapies that work by targeting the programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) pathway — were approved by the FDA for the treatment of urothelial carcinoma in 2016 and 2017, respectively. 

The FDA based its recommendations on preliminary findings from two ongoing clinical studies. In the phase 3 KEYNOTE-361 (ClinialTrials.gov Identifier: NCT02853305) study, patients were randomly assigned to receive pembrolizumab with or without chemotherapy, or chemotherapy alone.2The Independent Data Monitoring Committee (iDMC) found that patients who were classified as having a low (<10%) combined positive score, a measure of PD-L1 expression, receiving pembrolizumab alone had poorer survival compared with patients receiving platinum-based chemotherapy.

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Similar outcomes were observed in the phase 3 IMVIGOR-130 (ClinicalTrials.gov Identifier: NCT02807636) study.3Patients were randomly assigned to receive atezolizumab, atezolizumab plus chemotherapy, or chemotherapy alone. The iDMC discovered in a review of early data that patients with PD-L1 expression of less than 5% in the monotherapy arm also had reduced survival compared with those who received platinum-based chemotherapy. 

The iDMC recommended stopping the enrollment of patients with low PD-L1 expression into the monotherapy arms of both studies, but no other changes were recommended, including any changes in therapy for patients who were already enrolled into the monotherapy arms or receiving monotherapy. 

Analyses are ongoing, and any further updated data will be communicated by the FDA. 


  1. FDA Alerts Health Care Professionals and Oncology Clinical Investigators about an Efficacy Issue Identified in Clinical Trials for Some Patients Taking Keytruda (pembrolizumab) or Tecentriq (atezolizumab) as Monotherapy to Treat Urothelial Cancer with Low Expression of PD-L1 [news release]. Silver Spring, MD: US Food and Drug Administration; Updated June 20, 2018.https://www.fda.gov/Drugs/DrugSafety/ucm608075.htm. Accessed June 25, 2018. 
  2. Keytruda [package insert]. Whitehouse Station, NJ: Merck and Co., Inc.; 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125514s043lbl.pdf. Accessed June 25, 2018. 
  3. Tecentriq [package insert]. South San Francisco, CA: Genentech Inc.; 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761034s010lbl.pdf. Accessed June 25, 2018. 

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