FDA Identifies Efficacy Issue in Clinical Trials of Pembrolizumab or Atezolizumab as Monotherapy in Urothelial Cancer With Low Expression of PD-L1

On May 18, the U.S. Food and Drug Administration (FDA) alerted health-care professionals, oncology clinical investigators, and the public about decreased survival associated with the use of pembrolizumab (Keytruda) or atezolizumab (Tecentriq) as monotherapy in clinical trials to treat patients with metastatic urothelial cancer who have not received prior therapy and who have low expression of the protein programmed cell death ligand 1 (PD-L1).

In two ongoing clinical trials (KEYNOTE-361 and IMvigor130), early reviews by the respective data monitoring committees (DMCs) found patients in the monotherapy arms of both trials with PD-L1–low status had decreased survival compared to patients who received cisplatin- or carboplatin-based chemotherapy. There was no change in the adverse event profile of pembrolizumab or atezolizumab. Both Merck, manufacturer of pembrolizumab, and Genentech, manufacturer of atezolizumab, have stopped enrolling patients whose tumors have PD-L1–low status to the pembrolizumab or atezolizumab monotherapy arms per the DMCs’ recommendations.

The clinical trials compare platinum-based chemotherapy combined with pembrolizumab or atezolizumab to platinum-based chemotherapy alone. Both trials enrolled a third arm of monotherapy with pembrolizumab or atezolizumab to compare to platinum-based chemotherapy alone. The monotherapy arms remain open only to patients whose tumors have PD-L1–high status. The combination arms and the chemotherapy arms of both studies also remain open. The FDA is reviewing the findings of the ongoing clinical trials and will communicate new information as necessary.

Current Approvals

Both pembrolizumab or atezolizumab are currently approved under accelerated approval for the treatment of locally advanced or metastatic urothelial carcinoma patients who are not eligible for cisplatin-containing chemotherapy, irrespective of PD-L1 status. Patients taking pembrolizumab or atezolizumab for other approved uses should continue to take their medication as directed by their health-care professional.

Health-care professionals should be aware that the populations enrolled in the ongoing clinical trials were eligible for platinum-containing chemotherapy, and therefore differ from those enrolled in the trials that led to the accelerated approvals of both pembrolizumab and atezolizumab in the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy. The FDA recommends providers select patients for the treatment of locally advanced or metastatic urothelial cancer using the criteria described in Section 14 of each label. These criteria supported the approvals for pembrolizumab and atezolizumab for initial monotherapy in cisplatin-ineligible patients. Pembrolizumab and atezolizumab are also currently approved by the FDA for the treatment of multiple types of other cancers.

Health-care professionals and patients are encouraged to report any adverse events or side effects related to the use of these products and other similar products to FDA’s MedWatch Adverse Event Reporting program.

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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