• Matthew Stachowiak

PD-L1 Companion Diagnostics and Scoring Systems

Updated: Aug 27, 2020

FDA Approvals with PD-L1 Companion Diagnostics

Recently, FDA approved two new immunotherapies with PD-L1 based companion diagnostics, both for the first-line treatment of metastatic non-small cell lung cancer (NSCLC).

(1) Combination therapy nivolumab + ipilimumab, for PD-L1 expression >= 1%, and

(2) atezolizumab for high expression of PD-L1 (IC >= 10% or TC >= 50%)

Prior to these approvals, pembrolizumab was the only drug with a PD-L1 based companion diagnostic in NSCLC (based on TPS score >= 1%).

Previously, atezolizumab had PD-L1 based companion diagnostic for two other diseases -- urothelial carcinoma and triple negative breast cancer. Also, atezolizumab (in combination with chemotherapy), nivolumab, and nivolumab + ipilimumab had other approvals for NSCLC, but these were all regardless of PD-L1 expression levels.

The following table shows the new set of PD-L1 companion diagnostics and associated scoring systems as of 5/31/2020:

There are now three therapies with five different scoring systems for PD-L1 companion diagnostics. Three of the scoring systems are based on the percentage of tumor cells with PD-L1 staining (TPS, TC, % PD-L1 Expression), and seem to have equivalent definitions. IC is based on PD-L1 expression in tumor-infiltrating immune cells, while CPS (the only scoring system that is a number rather than a percentage) counts PD-L1 staining in both tumor cells and non-tumor cells.

Combined PD-L1 and NGS reporting

In my experience, most often PD-L1 results are reported and interpreted separately from NGS results. However, at GenomOncology, a growing number of our clients combine PD-L1 results and NGS results into a single report. This has a few advantages:

  1. Simplicity. A single report with a unified interpretation.

  2. Individual therapy indications involve both PD-L1 and NGS results. For example, both new approvals for NSCLC (atezolizumab and nivolumab + ipilimumab) require the tumor to be negative for ALK fusion and EGFR mutations, in addition to the companion diagnostic requirement for PD-L1.

  3. Therapy selection depends on synthesizing PD-L1 and NGS results. Even when a patient is eligible for an immune checkpoint inhibitor according to the FDA label (e.g. PD-L1 expression + ALK negative + EGFR negative), if there is another oncogenic driver present such as BRAF V600E, ROS1/RET fusion, or MET exon 14 skipping, NCCN Guidelines recommend selecting a therapy based on that driver, instead of treating with the immune checkpoint inhibitor. A combined report can better convey this information.

PD-L1 Scores in Decision Support Software

In order to support our clients who report PD-L1 alongside NGS results, GenomOncology software handles PD-L1 scoring. The PD-L1 result for a given assay can be expressed as a single "alteration concept" that includes both the scoring system and the measured score result. For example:

  • PD-L1 Expression (TPS = 60%)

  • PD-L1 Expression (CPS = 3)

  • PD-L1 Expression (IC = 8%)

Our content team curates "therapy assertions" that indicate the range of valid scores. For example, this is a screenshot of the PD-L1 based pembrolizumab approval for HNSCC:

The GenomOncology Match Algorithm then ensures that any particular PD-L1 result matches properly to the appropriate therapies.

Please reach out to with any questions.

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