Abstract 5859: Genomic correlates of response to immune checkpoint inhibitors in advanced head and neck squamous cell carcinoma

e18527 Background: Biomarkers for response prediction to immune checkpoint inhibitors in head and neck squamous cell carcinoma (HNSCC) patients are needed for a personalized therapy regimen. Therefore, we investigated the predictive potential of inflammatory biomarkers and DNA methylation. Methods: We profiled the methylation status of 850.000 CpG sites in formalin-fixed, paraffin-embedded primary HNSCC samples collected before ICI therapy start using Infinium Methylation EPIC microarrays. Tumor-infiltrating lymphocytes (TILs) and programmed cell death ligand 1 (PD-L1) expression were analyzed employing immunohistochemistry staining. Methylation profile, TIL density and PD-L1 expression were correlated with best radiological response to ICI treatment. Results: 29 patients (median age of 61; range 28-80) years; 8 (27.6%) females, 21 (72.4%) males) with HNSCC were included. Median number of prior systemic therapies was 1 (range 0-3). Median number of ICI applications was 6 (range 1-45). 2/29 (6.9%) patients achieved an objective response (complete response or partial response) under anti-PD-1 therapy. Median progression-free survival (PFS) and median overall survival (OS) were 3.3 months (range 0-28.8) and 7.2 months (range 0-29.4), respectively. 7/29 (24.1%) patients were still alive and one of these patients was still on ICI therapy at data cut-off. Methylation analyses revealed a combination of methylation changes (both hypo- and hypermethylation) that was predictive for response to ICI. 11/27 (40.7%) patients had PD-L1 expressing tumor cells ( > 1% PD-L1 expression). Median density of CD8+ TILs was 423.49 cells/mm2 tumor (range 5.71-11528.43 cells/mm2) and median density of CD3+ TILs was 794.82 cells/mm2 tumor (range 1.68-8811.74 cells/mm2). There was no correlation of PD-L1 expression, density of CD8+ or CD3+ TILs with response or disease control (p > 0.05). Conclusions: In contrast to PD-L1 expression and TIL density, methylation profiles were associated with response to ICI treatment in HNSCC patients.

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Immune checkpoint inhibitors for head and neck squamous cell carcinoma: Current landscape and future directions

Head & Neck ◽

10.1002/hed.25930 ◽

2019 ◽

Vol 41 (S1) ◽

pp. 4-18 ◽

Cited By ~ 4

Author(s):

Hsiang‐Fong Kao ◽

Pei‐Jen Lou

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Neck Squamous Cell Carcinoma ◽

Future Directions

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Patterns of Response to Immune Checkpoint Inhibitors in Association with Genomic and Clinical Features in Patients with Head and Neck Squamous Cell Carcinoma (HNSCC)

Cancers ◽

10.3390/cancers13020286 ◽

2021 ◽

Vol 13 (2) ◽

pp. 286

Author(s):

Panagiota Economopoulou ◽

Maria Anastasiou ◽

George Papaxoinis ◽

Nikolaos Spathas ◽

Aris Spathis ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Tumor Growth ◽

Cell Carcinoma ◽

Head And Neck ◽

Gene Amplification ◽

Squamous Cell ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Neck Squamous Cell Carcinoma

Background: We sought to compare patterns of response to immune checkpoint inhibitors (ICI) with respect to clinical and genomic features in a retrospective cohort of patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Methods: One hundred seventeen patients with R/M HNSCC treated with ICI were included in this study. Tumor growth kinetics (TGK) prior to and TGK upon immunotherapy (IO) was available for 49 patients. The TGK ratio (TGKR, the ratio of tumor growth velocity before and upon treatment) was calculated. Hyperprogression (HPD) was defined as TGKR ≥ 2. Results: HPD was documented in 18 patients (15.4% of the whole cohort). Patients with HPD had statistically significant shorter progression free survival (PFS) (median PFS 1.8 months (95% CI, 1.03–2.69) vs. 6.1 months for patients with non-HPD (95% CI, 4.78–7.47), p = 0.0001) and overall survival (OS) (median OS 6.53 months (95% CI, 0–13.39) vs. 15 months in patients with non HPD (95% CI, 7.1–22.8), p = 0.0018). In a multivariate Cox analysis, the presence of HPD remained an independent prognostic factor (p = 0.049). Primary site in the oral cavity and administration of ICI in the second/third setting were significant predictors of HPD in multivariate analysis (p = 0.028 and p = 0.012, respectively). Genomic profiling revealed that gene amplification was more common in HPD patients. EGFR gene amplification was only observed in HPD patients, but the number of events was inadequate for the analysis to reach statistical significance. The previously described MDM2 amplification was not identified. Conclusions: HPD was observed in 15.4 % of patients with R/M HNSCC treated with IO and was associated with worse PFS and OS. EGFR amplification was identified in patients with HPD.

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Biomarkers for Immune Modulatory Treatment in Head and Neck Squamous Cell Carcinoma (HNSCC)

Critical Issues in Head and Neck Oncology ◽

10.1007/978-3-030-63234-2_6 ◽

2021 ◽

pp. 83-91

Author(s):

Danny Rischin

Keyword(s):

Squamous Cell Carcinoma ◽

T Cells ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Predictive Biomarkers ◽

Neck Squamous Cell Carcinoma

AbstractImmune checkpoint inhibitors have changed the standard of care for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, only a minority of patients respond, hence the search for predictive biomarkers. Potential predictive biomarkers for immune checkpoint inhibitors discussed in this chapter include (1) Immune checkpoint ligand expression e.g., PD-L1, (2) biomarkers of a T-cell inflamed tumour microenvironment (TME) such as gene expression profiles of activated T cells, (3) biomarkers of tumour neoepitope burden such as tumour mutation burden (TMB) and (4) multidimensional quantitative techniques. At present only PD-L1 expression has been shown to have clinical utility in head and neck cancer. It enriches for populations more likely to respond, but the false positive predictive value remains high. In the pivotal Keynote−048 trial that established a role for pembrolizumab (anti-PD1) monotherapy and pembrolizumab + chemotherapy as treatment options in first-line R/M HNSCC, primary endpoints included overall survival in defined subgroups based on PD-L1 expression. In this trial the combined positive score (CPS) was used which takes into account PD-L1 expression in tumour and immune cells. Based on this trial regulatory approvals for first-line pembrolizumab in R/M HNSCC require assessment of PD-L1 expression using the CPS. Finally we discuss emerging evidence that locoregionally advanced HPV-associated oropharyngeal cancers that have high expression of CD103 positive CD8 T cells have an excellent prognosis and features that suggest increased probability of responding to anti-PD1/PD-L1, raising the possibility of incorporating these immune therapies as part of a de-escalation trial strategy.

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