107P - Association of tumor and stroma PD-1, PD-L1, CD3, CD4 and CD8 expression with response to nivolumab treatment in NSCLC patients

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Cancer in Adolescents
Biomarkers
Non-Small-Cell Lung Cancer, Metastatic
Cancer Immunology and Immunotherapy
Lung and other Thoracic Tumours
Translational Research
Presenter Sara Sahba
Citation Annals of Oncology (2017) 28 (suppl_5): v22-v42. 10.1093/annonc/mdx363
Authors S. Sahba1, A. Niemeijer1, J. De Langen1, E. Thunnissen2
  • 1Pulmonology, Vrije University Medical Centre (VUMC), 1081 HV - Amsterdam/NL
  • 2Pathology, Vrije University Medical Centre (VUMC), 1081 HV - Amsterdam/NL

Abstract

Background

PD-L1 immunohistochemistry (IHC) correlates only moderately with response to nivolumab treatment. Characterizing PD-1, PD-L1 and T-cell markers in both tumor and stroma might improve the predictive value of tissue IHC as predictive biomarker in this setting.

Methods

From 08-2015 to 12-2016 patients with stage IV NSCLC treated with nivolumab were registered and prospectively followed. A histological tumor biopsy, obtained before start of nivolumab, was required. Tumor PD-L1 expression and immune cell (IC) PD-L1, PD-1, CD3, CD4 and CD8 expression in tumor and stroma was assessed using IHC on serial sections. IC infiltration was scored semi-quantitatively indicating no, very low, low, intermediate, or high infiltration. Presence of CD4+ macrophages in between tumor cells was used to aid assessment of tumor PD-L1 expression. Nivolumab was dosed 3 mg/kg Q2W and response assessment was done by CT every six weeks.

Results

Overall response rate of pts (n = 65) was 23% and quantifiable (≥1%) tumor PD-L1 expression was found in 25% of pts, versus 50%) and associated response rates of 17%, 22% and 57% respectively. Stromal IC expression of PD-L1, CD3, CD4 and CD8 also correlated with response (p 

Conclusions

A clear positive correlation was found between PD-L1 expression and response. The distribution of PD-L1 expression was lower compared to historical data. Availability of CD4 IHC that identified PD-L1 positive macrophages is the explanation for lower percentage of tumor PD-L1 positive samples. Stromal PD-L1, CD3, CD4 and CD8 IC expression were all predictive for treatment response. In tumor PD-L1 negative pts, high stromal PD-L1 and/or CD3 IC expression selected pts with a remarkably high response rate.

Clinical trial identification

Legal entity responsible for the study

A. J. de Langen

Funding

VU University Medical Center, Department of Pulmonology

Disclosure

All authors have declared no conflicts of interest.