Biomarkers in cancer immunotherapy: Analysis of clinical, histological and immunohistochemical factors associated with PD-L1 status

Background: Inhibitors of PD-1/PD-L1 have changed the treatment paradigm in oncology. However, only a minority of patients respond to these therapies and therefore there is a critical need to identify molecular predictors that can help select patients to avoid unnecessary costs and toxicities. PD-L1 expression, detected by immunohistochemistry is currently the most explored biomarker, but its predictive value is still unclear. Methods: Between January 2014 and July 2015, 346 patients were candidate for treatment with anti-PD-1/PD-L1 antibodies (pembrolizumab P, durvalumab D or atezolizumab A) at Gustave Roussy Cancer Campus.We reviewed in detail the files of 309 patients for whom PD-L1 expression could have been measured. Clinical, histological and IHC features were retrospectively collected for all of them in order to identify factors affecting PD-L1 status. Results: 83 patients (26.9%) were positive for PD-L1 in IHC. PD-L1 positivity varied significantly depending on the treatment considered: P = 32.9%; D= 30.5% et A = 11.5% (p = 0.002). This suggests a relation between the companion test used for IHC and PD-L1 positivity. Univariate analysis showed that PD-L1 expression was associated with IHC test, primary tumor site and histological type. In multivariate analysis, IHC test and histological type remained significant (respectively p= 0.001 and 0.008). Atezolizumab companion test (SP142) was associated with low PD-L1 expression; while squamous cell carcinoma and urothelial carcinoma were associated with high expression. Among metastatic patients, samples from liver metastasis showed a trend for lower PD-L1 expression. There was no significant relationship with sampling method (biopsy or surgical resection), histological analysis place ( private or academic), sample size, age or cellularity, or sample location (primary or metastatic site). There was no difference between samples acquired before or after some anticancer treatment. Conclusions: This study identified that IHC test and histological type were associated with PD-L1 status, which need to be further investigated. The trend for lower PD-L1 expression in liver metastasis sample needs to be confirmed and compared with clinical response data.