Prognostic significance of PD-L1 expression on circulating tumor cells in patients with head and neck squamous cell carcinoma
Menée sur une cohorte de 113 patients atteints d'un carcinome épidermoïde de la tête et du cou de stade localement avancé, cette étude évalue la possibilité de mesurer, avant et durant le traitement, le niveau d'expression de l'ARN messager de PD-L1 dans les cellules tumorales circulantes exprimant EpCAM, puis évalue l'intérêt de cette mesure pour établir un pronostic
Background : Successful application of PD1 checkpoint inhibitors in the clinic may ultimately benefit from appropriate patient selection based upon predictive biomarkers. Molecular characterization of CTC is crucial for the investigation of molecular targeted therapies while predictive biomarkers for response to PD1 checkpoint inhibitors are lacking. We sought to assess whether overexpression of PD-L1 in CTCs could be detected at baseline and at different timepoints during treatment in a prospective cohort of HNSCC patients and used to predict clinical outcome after treatment with curative intent.
Patients and methods : We developed a highly sensitive, specific and robust RT-qPCR assay for PD-L1 mRNA expression in EpCAM(+) CTCs. In a prospective cohort of 113 locally advanced HNSCC patients treated with curative intent we evaluated PD-L1 expression in the EpCAM(+) CTC fraction at baseline, after 2 cycles of induction chemotherapy (IC) (week 6) and at the end of concurrent chemoradiotherapy (week 15).
Results :PD-L1 overexpression was found in 24/94 (25.5%) patients at baseline, 8/34 (23.5%) after IC and 12/54(22.2%) patients at the end of treatment. Patients with CTCs overexpressing PD-L1 at end of treatment had shorter progression-free survival (PFS) (p=0.001) and overall survival (OS) (p<0.001). Multivariate analysis revealed that PD-L1 overexpression at end of treatment was independent prognostic factor for PFS and OS. The absence of PD-L1 overexpression at the end of treatment was strongly associated with complete response with an odds ratio=16.00 (95%CI=2.76-92.72, p=0.002).
Conclusions : We demonstrate that detection of CTCs overexpressing PD-L1 is feasible and may provide important prognostic information in HNSCC. Our results suggest that adjuvant PD1 inhibitors deserve evaluation in HNSCC patients in whom PD-L1(+) CTCs are detected at the end of curative treatment.
Annals of Oncology , résumé, 2016