FDA safety alert: use of immunotherapy in metastatic urothelial cancer with low PD-L1 expression.

On May 18, the United States (US) Food and Drug Administration (FDA) issued an alert about the decreased survival in studies with pembrolizumab (Keytruda®) and atezolizumab (Tecentriq®) as single agent first-line therapy for patients with metastatic urothelial cancer (mUCC) and low expression of the programmed death ligand 1 (PD-L1) protein.

The alert is based on two ongoing clinical trials, the KEYNOTE-361 with pembrolizumab and the IMvigor130 with atezolizumab. An early review by the study’s Data Monitoring Committees revealed that patients in the monotherapy arms and low PD-L1 level expression had decreased survival compared to patients who received platinum-based chemotherapy with either cisplatin or carboplatin.

The US FDA noted that the populations enrolled in the KEYNOTE-361 and IMvigor130 studies are outside the US FDA approved label for both drugs. Patients enrolled in the study were candidates for platinum-based chemotherapy, whereas the approved US FDA label for atezolizumab and pembrolizumab includes only patients pretreated with a platinum-containing regimen or ineligible for cisplatin-based chemotherapy.

The US FDA recommends healthcare providers to prescribe drugs only according to the approved indications.