From the Guidelines
PD-L1 Combined Positive Score (CPS) is a scoring system used to measure PD-L1 expression in tumor tissue samples, calculated by dividing the number of PD-L1-staining cells by the total number of viable tumor cells, then multiplying by 100, with a score of 1 or greater often considered positive for PD-L1 expression, as seen in studies such as 1. The CPS score is crucial in determining which patients are likely to respond to immunotherapy treatments, particularly immune checkpoint inhibitors like pembrolizumab. Key points to consider when interpreting PD-L1 CPS include:
- The score is calculated by dividing the number of PD-L1-staining cells (tumor cells, lymphocytes, and macrophages) by the total number of viable tumor cells, then multiplying by 100, as described in 1.
- A higher PD-L1 CPS score generally indicates a greater likelihood of response to immunotherapy treatments, as noted in 2 where patients with tumor CPS ≥ 1 had an ORR of 33.3% compared to 10.3% for those with CPS < 1.
- The score is important because PD-L1 expression indicates that cancer cells are using this pathway to evade the immune system, and blocking this interaction with immunotherapy can potentially restore anti-tumor immune responses.
- Pathologists determine this score through immunohistochemistry staining of tumor biopsy samples, and different assays can yield different results, as discussed in 1. In clinical practice, a PD-L1 CPS score of 1 or greater may qualify patients for immunotherapy treatment, as seen in certain cancers like head and neck squamous cell carcinoma or gastric cancer, and the FDA has approved pembrolizumab in combination with chemotherapy for treatment of triple-negative breast cancer that has tested positive for PD-L1 using the specific 22C3 companion assay, with a positive definition of a CPS of at least 10, as mentioned in 1.
From the FDA Drug Label
A retrospective scoring of a patient’s tumor PD-L1 status using Combined Positive Score (CPS), was also conducted using the PD-L1-stained tumor specimens used for randomization. The Combined Positive Score (CPS) is a measure of tumor PD-L1 status, but the exact definition or calculation of CPS is not provided in the drug label. 3
- The label only mentions that a retrospective scoring of CPS was conducted, but it does not provide further information on how CPS is calculated or what it represents.
- Therefore, no conclusion can be drawn about the exact definition or calculation of CPS.
From the Research
Definition of PD-L1 Combined Positive Score
- The Combined Positive Score (CPS) is a method of evaluating Programmed Death-Ligand 1 (PD-L1) expression in tumors, which takes into account both tumor and immune cells 4, 5, 6.
- CPS is calculated by adding the number of PD-L1-positive tumor cells and immune cells, then dividing by the total number of tumor cells and multiplying by 100 6.
Clinical Utility of CPS
- CPS has been shown to be a useful biomarker for predicting response to immune checkpoint inhibitors, such as pembrolizumab, in patients with various types of cancer, including gastric cancer and head and neck cancer 4, 5, 6.
- A CPS score of 1 or more has been used as a cutoff to identify patients who are likely to respond to pembrolizumab therapy 6.
- Studies have also explored the use of higher CPS scores, such as 50 or 70, as potential predictors of improved response to therapy 4, 5.
Comparison with Other Scoring Methods
- CPS has been compared to other scoring methods, such as the Tumor Proportion Score (TPS), which only evaluates PD-L1 expression in tumor cells 5, 7.
- Studies have shown that CPS may be more sensitive than TPS at lower cutoffs, and that CPS ≥ 50 may be equivalent to TPS ≥ 50% for predicting response to pembrolizumab 5.