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Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

3071 - PD-L1 expression on pre-treatment circulating tumour cells, but not serum VEGF, is predictive of response to pembrolizumab in melanoma

Date

20 Oct 2018

Session

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

Presenters

Muhammad Khattak

Citation

Annals of Oncology (2018) 29 (suppl_8): viii14-viii57. 10.1093/annonc/mdy269

Authors

M.A. Khattak1, E.S. Gray2, A. Reid2, M. Periera2, A. McEvoy2, C. Aya-Bonilla2, T. Meniawy3, A. Didan1, M. Millward3, M. Ziman2

Author affiliations

  • 1 Medical Oncology, Fiona Stanley Hospital, 6150 - Perth/AU
  • 2 School Of Medical And Health Sciences, Edith Cowan University, 6027 - Perth/AU
  • 3 Oncology, School of Medicine and Pharmacology Sir Charles Gairdner Hospital, 6009 - Nedlands/AU
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Resources

Abstract 3071

Background

Immune checkpoint inhibitors including pembrolizumab and nivolumab have revolutionised treatment of melanoma with a small proportion of patients deriving durable disease control lasting up to 5 years. However, majority of patients do not respond to these drugs that are costly and can lead to substantial toxicity. Therefore, there is an urgent need for biomarkers that can identify patients that will respond to these therapies.

Methods

We used multi-parametric flow cytometry to identify circulating tumour cell (CTC) subpopulations based on the expression of melanoma markers MCAM, MCSP, ABCB5, CD271 and RANK in metastatic melanoma patients prior to commencing treatment with pembrolizumab (n = 40) or with ipilimumab alone or in combination with nivolumab (n = 14). In particular, we evaluated the expression of PD-L1 on CTCs in relation with response to treatment and progression free survival (PFS). Serum vascular endothelial growth factor (VEGF) concentrations were also evaluated.

Results

Pre-treatment serum VEGF concentrations were significantly higher in patients not responding to ipilimumab treatment (alone or in combination with nivolumab) (p = 0.0094). In contrast, serum VEGF was not predictive of response to pembrolizumab. Pre-treatment CTC positivity was not associated with response or PFS in either cohorts. However, PD-L1 expression on CTCs was associated with response to therapy. PD-L1 expression was found in 13 of 16 responders with detectable CTCs, while only 4 of 10 non-responders had PD-L1 detectable on their CTCs (p = 0.0425). Expression of PD-L1 on CTCs was also associated with longer PFS (p = 0.0117).

Conclusions

Our results provide evidence for the first time in melanoma, that detection of PD-L1 on CTCs is predictive of response to pembrolizumab and longer PFS.

Clinical trial identification

Legal entity responsible for the study

Research Governance Office Sir Charles Gairdner Hospital and Fiona Stanley Hospital.

Funding

MSD.

Editorial Acknowledgement

Disclosure

M.A. Khattak, M. Ziman: Research grant: MSD. All other authors have declared no conflicts of interest.

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