On 16 August 2018, the US Food and Drug Administration (FDA) updated the prescribing information for pembrolizumab (Keytruda) and atezolizumab (Tecentriq) to require the use of an FDA-approved companion diagnostic test to determine PD-L1 levels in tumour 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.
On 16 August 2018, the 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 (CPS) assessing PD-L1 staining in tumour 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 tumours express PD-L1 (CPS ≥ 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.
On 2 July 2018, the 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 tumours express PD-L1 (PD-L1 stained tumour-infiltrating immune cells [IC] covering ≥5% of the tumour area), as determined by an FDA-approved test, or
- Are not eligible for any platinum-containing therapy regardless of level of tumour 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.
Prescribing information for Keytruda is available here and for Tecentriq here.