FDA Warns Efficacy Concerns in Some Patients Taking Keytruda, Tecentriq

In a statement released yesterday, the FDA has announced that it is restricting the use of pembrolizumab (Keytruda) and atezolizumab (Tecentriq) for patients with locally advanced or metastatic urothelial cancer who are not eligible for cisplatin-containing therapy.

The FDA made this decision based on data that showed decreased survival associated with each drug as a monotherapy compared with platinum-based chemotherapy in clinical trials that were investigating the drugs ability to treat metastatic urothelial cancer patients who have not received prior therapy and who have low expression of PD-L1.

In 2 ongoing clinical trials, KEYNOTE-361 and IMVIGOR-130, the Data Monitoring Committees’ (DMC) early reviews found patients receiving the drugs as monotherapies with PD-L1 low status had decreased survival compared with patients that received cisplatin or carboplatin-based chemotherapy. In May 2018, the FDA alerted healthcare professionals and oncology clinical investigators to these initial findings.

The trials looked to compare platinum-based chemotherapy combined with either pembrolizumab or atezolizumab to evaluate the efficacy of platinum-based chemotherapy alone. Both drug manufacturers, Merck and Genentech respectively, have stopped enrolling patients whose tumors express low PD-L1 to the monotherapy arms of the trials.

Both pembrolizumab and atezolizumab were approved under the FDA’s accelerated approval pathway to treat urothelial carcinoma patients who are not eligible for cisplatin-containing chemotherapy, regardless of PD-L1 status.

As of last week, pembrolizumab had earned its 11th indication with the approval to treat recurrent or metastatic cervical cancer with disease progression on or after chemotherapy in patients whose tumors express PD-L1. Atezolizumab only holds 1 other indication for the treatment of patients with previously treated metastatic non-small cell lung cancer.

“The FDA has not changed the indications of Keytruda and Tecentriq 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,” the FDA said in a statement.