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Poster Discussion – Head and neck cancer

2016 - High Immunoscore is associated with good response to neo-adjuvant chemotherapy and prolonged survival in advanced Head and Neck cancer patients.

Date

28 Sep 2019

Session

Poster Discussion – Head and neck cancer

Presenters

Haitham Mirghani

Citation

Annals of Oncology (2019) 30 (suppl_5): v449-v474. 10.1093/annonc/mdz252

Authors

H. Mirghani1, C. Mure2, B. Mlecnik3, F. Hermitte4, E. Martel5, O. Casiraghi5, M. Iacob1, C. Even6, J. Galon7

Author affiliations

  • 1 Department Of Head And Neck Oncology, Gustave Roussy Cancer Center, 94805 - Villejuif/FR
  • 2 Department Of Head And Neck Oncology, Gustave Roussy Cancer Cente, 94805 - Villejuif/FR
  • 3 Laboratory Of Integrative Cancer Immunology, Inserm, 75006 - Paris/FR
  • 4 Medical Affairs, HalioDx, 13009 - Marseille/FR
  • 5 Department Of Pathology, Gustave Roussy Cancer Center, 94805 - Villejuif/FR
  • 6 Department Of Head And Neck Oncology, Institut Gustave Roussy, 94805 - Villejuif/FR
  • 7 Inserm Team 15, Laboratory of Integrative Cancer Immunology, 75006 - Paris/FR

Resources

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Abstract 2016

Background

The presence of high levels of tumor immune infiltrate has been recognized to be associated with better prognosis in Head and Neck cancer (H&N). The consensus Immunoscore quantifies the densities of CD3 and CD8 in the center of the tumour (CT) and the invasive margin (IM) and stratifies patients into 3 Immunoscore categories (Low, Intermediate and High).

Methods

This retrospective ongoing study evaluated the Immunoscore in 110 patients with advanced laryngeal (n = 57) or hypopharyngeal (n = 53) cancers who received neo-adjuvant chemotherapy in the setting of an organ preservation protocol. Good responders (tumor reduction > 50%) were subsequently treated by radiation/chemoradiation, whereas non-responders were subjected to surgery followed by post-operative radiation/chemoradiation. Pre-treatment tumor samples were immune-stained for T-cell (CD3, CD8) markers and quantitative analysis of the immune cells was carried out in different tumor locations using a computer-assisted image analysis.

Results

60% of patients were good responders. Densities of T cell infiltration were significantly higher for Hypopharyngeal cancer patients compared to those with laryngeal cancer. ( P < 0.001) Analysis of the entire cohort showed that good-responders had a higher Immunoscore than non-responders (69% vs. 39%% respectively, Odd Ratio = 2.7303 CI 95%[0.8497-9.24], P = 0.069). Immunoscore Low, Intermediate and High represented respectively 16.5%, 45.6% and 37.9% of the cohort. High Immunoscore patients were at low risk of relapse, with 5-year Time to Recurrence rates of 71.4 (CI 53.9 − 94.6) as compared to 54.6 CI 95% (40.4 − 73.9) and 31.4 CI 95% (13.3 − 74.1) in intermediate and low Immunoscore patients respectively (HR = 1.9 CI 95% (1.2 − 3.0), P < 0.02). Similar results were found in Larynx and Hypopharynx separately. Regardless of treatment type and tumor location, a high Immunoscore was associated with better progression-free survival and overall survival.Table: 1115PD

CutpointSensitivitySpecificityN (prevalence)ORR, %Odds Ratio (CI)PFS HR (CI)OS HR (CI)
TPS ≥50%0.470.7765 (0.27)26.23.83 (1.31, 11.15)0.59 (0.40, 0.87)0.54 (0.36, 0.82)
TPS ≥20%0.560.6494 (0.39)21.31.84 (0.83, 4.11)0.72 (0.52, 0.99)0.66 (0.47, 0.93)
TPS ≥1%0.640.44140 (0.57)16.41.56 (0.79, 3.10)0.95 (0.74, 1.22)0.75 (0.57, 0.97)
CPS ≥500.500.7864 (0.26)28.14.70 (1.62, 13.59)0.60 (0.41, 0.89)0.60 (0.40, 0.91)
CPS ≥200.580.6496 (0.39)21.92.42 (1.10, 5.33)0.75 (0.55, 1.01)0.63 (0.46, 0.86)
CPS ≥10.940.23195 (0.80)17.41.85 (1.01, 3.37)0.89 (0.72, 1.11)0.72 (0.58, 0.91)
All1.000.00244 (1.00)14.81.43 (0.83, 2.46)0.94 (0.77, 1.14)0.79 (0.65, 0.97)

CPS, combined positive score; HR, hazard ratio; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; SOC, standard of care; TPS, tumor proportion score.

Sensitivity, specificity, N (prevalence), and ORR are for the pembrolizumab arm. Odds ratio, PFS HR, and OS HR compare pembrolizumab and SOC.

Conclusions

The results of this ongoing study show a significant prognostic and potentially predictive role of Immunoscore in H&N cancer patients with important therapeutic implications.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Haitham Mirghani.

Funding

HalioDx.

Disclosure

H. Mirghani: Advisory / Consultancy: MSD vaccin; Travel / Accommodation / Expenses: BMS. B. Mlecnik: Licensing / Royalties: HalioDx. F. Hermitte: Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: HalioDx. C. Even: Advisory / Consultancy: MSD; Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Serono; Advisory / Consultancy: Innate Pharma; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca. J. Galon: Advisory / Consultancy, Research grant / Funding (institution), Shareholder / Stockholder / Stock options: HalioDx; Honoraria (self): AstraZeneca; Honoraria (self): Novartis; Honoraria (self): Merck Serono; Honoraria (self): MSD; Honoraria (self): BMS; Honoraria (self): Sanofi; Honoraria (self): Gilead; Advisory / Consultancy, Research grant / Funding (institution): IOBiotech; Advisory / Consultancy: Illumina; Advisory / Consultancy: Northwest Biotherapeutics; Advisory / Consultancy: Actelion; Advisory / Consultancy: Amgen; Research grant / Funding (institution): Perkin-Helmer; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Imcheck; Licensing / Royalties: Inserm. All other authors have declared no conflicts of interest.

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