FDA Restricts Use of Keytruda, Tecentriq in Certain Patients Due to Efficacy Issues

Officials with the FDA are restricting the use of pembrolizumab (Keytruda, Merck) and atezolizumab (Tecentriq) in certain patients with urothelial cancer due to an efficacy issue identified in clinical trials.

According to the safety alert, the new indication restricts use of pembrolizumab and atezolizumab for patients with locally advanced or metastatic urothelial cancer who are not eligible for cisplatin-containing therapy. The labels of both drugs have been revised to reflect the restricted indications.

In May 2018, the FDA alerted health care professionals and oncology clinical investigators about decreased survival associated with the use of pembrolizumab and atezolizumab as a single therapy in trials to treat patients with metastatic urothelial cancer who have a low expression of programmed death ligand 1 (PD-L1).

In 2 ongoing clinical trials, patients in the monotherapy arms of both trials with PD-L1 low status had decreased survival compared with patients who received cisplatin- or carboplatin-based chemotherapy. Both manufacturers have stopped enrolling patients whose tumors have PD-L1 low status in the monotherapy arms.

Pembrolizumab is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing therapy and whose tumors express PD-L1, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1.

Atezolizumab is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing therapy, whose tumors express PD-L1, and who are not eligible for any platinum-containing therapy regardless of the level of tumor PD-L1 expression.

The FDA has not changed the indications for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following any platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant treatment.

Additionally, continuation of treatment could be considered in patients already receiving pembrolizumab or atezolizumab who are responding to treatment and are cisplatin-ineligible, regardless of PD-L1 status.

According to the FDA, patients taking pembrolizumab or atezolizumab for other approved uses should continue to take their medication as directed by their health care professional. The FDA is reviewing the findings of ongoing analyses regarding the PD-L1 assays and will communicate new information as it becomes available.

Reference

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 [safety alert]. FDA’s website. https://www.fda.gov/Drugs/DrugSafety/ucm608075.htm. Accessed June 21, 2018.