In March 2019, the FDA approved atezolizumab (Tecentriq^®), the first PD-1/PD-L1 immune checkpoint inhibitor for metastatic triple-negative breast cancer, based on the IMpassion130 study. To qualify for atezolizumab immunotherapy, the cancer must also test positive for the PD-L1 protein.

This new approval brings immunotherapy to the landscape of MBC treatment. But there are still many questions. One important question is whether a PD-L1 test alone can adequately identify people who can benefit from atezolizumab and other PD-1/PD-L1 immune checkpoint inhibitors.

To get an understanding of the problem of using only PD-L1 positivity to identify people who may benefit from immune checkpoint inhibitors, and current research on how oncologists can identify people suited for immunotherapy, see the links below.

The Basics of PD-1 and PD-L1

• PD-L1/PD-1 Pathway: A Security Checkpoint (Video) This animated video explains the PD-1/PD-L1 pathway, the role each plays in cancer development, and how immune checkpoint inhibitors help the immune system find and destroy cancer cells.

First Immunotherapy and PD-L1 Test Approved for MBC

• First Immunotherapy Approved for MBC  The April 2019 issue of Metastatic Trial Talk gives a good overview of the IMPassion130 study findings that led to the FDA approval of atezolizumab in 2019.
• VENTANA PD-L1 SP142 Testing Assay  In breast cancer, atezolizumab is only approved for PD-L1 positive metastatic TNBC. To be prescribed atezolizumab you must get PD-L1 results using a specific lab test that the FDA approved, called the SP142 assay.

PD-L1 as the Single Biomarker for Immunotherapy: One Does Not Fit All

• IMPassion130 Trial: Changing the Treatment Landscape in Metastatic Triple-Negative Breast Cancer  The ASCO Post discusses why PD-L1 is not the perfect biomarker to determine who with metastatic breast cancer might respond well to PD-1/PD-L1 immune checkpoint inhibitors.
• ESMO Breast 2020: Novel Biomarkers May Predict Immunotherapy Benefit in Metastatic Breast Cancer  The ASCO Post summarizes research findings that alternative biomarkers may help better identify people most likely to benefit from immune checkpoint inhibitors. The article specifically discusses PD-L1 gene amplification and PD-L1 combined positive scores (CPS).
• Pembrolizumab (Keytruda ®) Biomarkers such as tumor mutation burden (TMB), microsatellite instability (MSI), or mismatch repair deficient (dMMR) have recently been approved by FDA to identify who can be treated with pembrolizumab (Keytruda^®), another FDA approved PD-1/PD-L1 immune checkpoint inhibitor.  (FDA updated approval)
• Expert Talks Immunotherapy for TNBC Treatment  Dr. Hope Rugo spoke with Oncology Nursing News about new research studying how to make tumors that are not initially responding to immunotherapy respond to it through treatment combinations.
• Like a Coin Flip™: Assay Denies Some Cancer Patients New Drug  Medscape digs into the complexities of PD-L1 testing, and why the results of the FDA approved test are sometimes incorrect. The PD-L1 test and the definition of PD-L1 positive may need to be improved.

Find Trials

• Metastatic Trial Search Find PD-L1-related clinical trials for advanced and metastatic breast cancer.