For patients with recurrent or metastasized squamous cell cancer of the head and neck (R/M SCCHN), the PD-L1 Combined Positive Score (CPS) is currently the only predictive biomarker for treatment with anti-PD-1 inhibitors. However, ambiguous results have been delivered regarding the overall response rate (ORR) of these immunotherapeutic agents. This issue may be attributed to the intratumoral, intertumoral and temporal heterogeneity of PD-L1 expression.
The concordance of PD-L1 CPS in and between primary tumors (biopsied and resected tissue) and paired metastatic lesions (lymph node or distant metastasis), respectively was investigated at bicategorical CPS cut-off (≥=1) and tricategorical CPS cut-offs (<1 / 1-19 / ≥=20). A total 147 tissue blocks from 67 SCCHN patients were collected. CPS agreement between specimens was evaluated using χ2 or Fisher's Exact testing.
Biopsies and paired resection material had discordant CPS for 36% and 44% of samples at bicategorical and tricategorical cut-offs, respectively. In paired primary tumor - metastatic lesions, disagreement was reached in up to 24% for bicategorical and 37% of tricategorical CPS. Additionally, paired tumor samples not exposed to intermittent radiochemotherapy showed a positive correlation between ∆CPS and ∆ time when adjusting for intratumoral heterogeneity, indicating PD-L1 expression may also be affected by temporal heterogeneity.
We observed discordance of PD-L1 CPS in over a third of paired specimens in and between primary tumor and metastatic material. Therefore, clinicians should always take notice of intratumoral, intertumoral and also temporal heterogeneity when assessing PD-L1 CPS, as this may lead to potential under- or overtreatment with pembrolizumab in patients with R/M SCCHN.
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MSD Belgium BV/SRL.
All authors have declared no conflicts of interest.