FDA has updated the prescribing information for Keytruda (pembrolizumab) and Tecentriq (atezolizumab) to require the use of an FDA-approved companion diagnostic test to determine PD-L1 levels in tumor tissue from patients with locally advanced or metastatic urothelial cancer who are cisplatin-ineligible. FDA approved two different companion diagnostic tests, one for use with Keytruda and one for use with Tecentriq, as described below.
FDA approved the Dako PD-L1 IHC 22C3 PharmDx Assay (Dako North America, Inc.) as a companion diagnostic to select patients with locally advanced or metastatic urothelial carcinoma who are cisplatin-ineligible for treatment with Keytruda. The 22C3 assay determines PD-L1 expression by using a combined positive score assessing PD-L1 staining in tumor and immune cells.
The updated indication for Keytruda is: Keytruda is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [Combined Positive Score ≥ 10] as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status.
FDA approved the Ventana PD-L1 (SP142) Assay (Ventana Medical Systems, Inc.) as a companion diagnostic test to select patients with locally advanced or metastatic urothelial carcinoma who are cisplatin-ineligible for treatment with Tecentriq. The SP142 assay determines PD L1 expression in immune cells.
The updated indication for Tecentriq is: TECENTRIQ is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who:
Are not eligible for cisplatin-containing chemotherapy, and whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells covering ≥5% of the tumor area), as determined by an FDA-approved test, or
Are not eligible for any platinum-containing therapy regardless of level of tumor PD-L1 expression
The FDA updated the prescribing information for both drugs to require use of an FDA-approved test for selection of patients being treated in the first-line setting who are cisplatin-ineligible. The second-line indications in urothelial carcinoma for both drugs remain unchanged. The tests used in the trials to determine PD-L1 expression are listed in Section 14 of each drug label.
