Journal
ONCOLOGIST
Volume 25, Issue 3, Pages E520-E527Publisher
WILEY
DOI: 10.1634/theoncologist.2019-0557
Keywords
Pembrolizumab; Melanoma; Immunotherapy; Circulating tumor cells
Categories
Funding
- National Health and Medical Research Council [1013349]
- Spinnaker Health Research Foundation
- MSD Investigator Studies Program
- Raine Foundation
- Cancer Research Trust
- Cancer Council of Western Australia
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Background PD-1 inhibitors are routinely used for the treatment of advanced melanoma. This study sought to determine whether PD-L1 expression on circulating tumor cells (CTCs) can serve as a predictive biomarker of clinical benefit and response to treatment with the PD-1 inhibitor pembrolizumab. Methods Blood samples were collected from patients with metastatic melanoma receiving pembrolizumab, prior to treatment and 6-12 weeks after initiation of therapy. Multiparametric flow cytometry was used to identify CTCs and evaluate the expression of PD-L1. Results CTCs were detected in 25 of 40 patients (63%). Patients with detectable PD-L1(+) CTCs (14/25, 64%) had significantly longer progression-free survival (PFS) compared with patients with PD-L1(-) CTCs (26.6 months vs. 5.5 months; p = .018). The 12-month PFS rates were 76% versus 22% in the PD-L1(+) versus PD-L1(-) CTCs groups (p = .012), respectively. A multivariate linear regression analysis confirmed that PD-L1(+) CTC is an independent predictive biomarker of PFS (hazard ratio, 0.229; 95% confidence interval, 0.052-1.012; p = .026). Conclusion Our results reveal the potential of CTCs as a noninvasive real-time biopsy to evaluate PD-L1 expression in patients with melanoma. PD-L1 expression on CTCs may be predictive of response to pembrolizumab and longer PFS. Implications for Practice The present data suggest that PD-L1 expression on circulating tumor cells may predict response to pembrolizumab in advanced melanoma. This needs further validation in a larger trial and, if proven, might be a useful liquid biopsy tool that could be used to stratify patients into groups more likely to respond to immunotherapy, hence leading to health cost savings.
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