Résumé
Purpose
Immune therapies, including anti-PD-L1 therapies, are widely evaluated in the treatment of solid tumors, including metastatic breast cancer (MBC). While tumor PD-L1 expression has been largely reported, with conflicting results regarding its theranostic value, few data are available regarding the prognostic value of the determination of PD-L1 expression on circulating tumor cells (CTCs), allowing a minimally invasive determination of this biomarker of interest. We previously published a validated and robust method for PD-L1(+)-CTC detection. In this new report, we focused on the clinicopathological correlations and prognostic value of the presence of PD-L1(+)-CTCs in an expanded MBC cohort.
Methods
We investigated PD-L1(+)-CTCs as previously reported (Mazel et al., Molecular Oncology, 9 (2015); 1773-1782) using the CellSearch® system in 72 MBC patients from our previous report and a prospective dedicated biomarker study (NCT02866149).
Results
Median age was 65 years (range 35-87). 69.4% of tumors were classified ER(+)/HER2(-), 18.1% HER2(+) and 12.5% triple negative (TN). 40 patients (55.6%) were treated in ≥ fourth metastatic line. 58.3% of the patients presented with more than 2 metastatic sites. Archival tissue was available for 56 patients (77.8%) and 13 samples (23.2%) showed positive (≥1%) PD-L1 expression. Baseline CTCs were detected in 57 patients (79.2%), with 43 (59.7%) and 36 (50%) patients with ≥4 and ≥10 CTCs, respectively. PD-L1(+)-CTCs were detected in 26 (36.1%) cases. No statistically significant correlation was found between PD-L1 tumor tissue expression and the presence of PD-L1(+)-CTCs (p=0.694). At the time of analysis, with a median follow-up of 13 months, 55 patients (76.4%) had progressed and 33 (45.8%) died.
Median progression-free survival (PFS) was 5 months (95%CI 3.5-8.0). In univariate analysis, TN phenotype (p=0.020), more than 3 previous metastatic treatment lines (p<0.001) and detection of PD-L1(+)-CTCs (p=0.047) were significantly associated with PFS, while it was not the case for the CTC count (≥4 CTCs threshold) or the PD-L1 expression in the biopsy (p=0.100 and p=0.280).
Median overall survival (OS) was 20 months (95%CI 11.1-38.3). In univariate analysis, TN phenotype (p=0.007) and the CTC count, either at the ≥4 (p=0.024) or ≥10 (p=0.027) threshold were significantly associated with OS, while there was a trend for association with OS of PD-L1(+)-CTCs detection (p=0.078).
Conclusion
In this heterogeneous MBC cohort, PD-L1 expression on CTCs appears independent of PD-L1 expressed in the primary tumor site. MBC patients harboring PD-L1(+)-CTCs seems to have a worse PFS. Evaluation of the respective impact of PD-L1 expression in the tumor and by CTCs is needed in a population treated by anti-PD-1/PD-L1 antibodies in order to evaluate their respective predictive values. An update of the OS data is warranted.
Citation Format: William Jacot, Martine Mazel, Caroline Mollevi, Stéphane Pouderoux, Véronique D'Hondt, Laure Cayrefourcq, Angélique Ducteil, Marie Viala, Thierry Maudelonde, Séverine Guiu, Catherine Alix-Panabières. Expression of PD-L1 on circulating breast cancer cells: Correlation with clinicopathologic data and impact on prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4589.