Abstract 1414: Treatment outcome under cetuximab-based therapy and individual ADCC capability in head and neck cancer

Abstract

Abstract Introduction Cetuximab is a IgG1 monoclonal antibody against epidermal growth factor receptor (EGFR) used for head and neck squamous cell carcinoma (HNSCC) treatment. In addition to EGFR targeting, cetuximab is able to develop an antibody-dependent cell-mediated cytotoxicity (ADCC), triggered by Fc receptors (Fcγ-R) on Natural Killer cells, macrophages and polymorphonucleated leukocytes. This prospective study examined the possible prognostic value of cetuximab-mediated ADCC response in a cohort of HNSCC patients. Patients and Methods There were 63 patients treated with curative intent with chemo-radiotherapy (CT-RT), associated (N = 39) or not (N = 24) with cetuximab. Peripheral blood samples were collected at start of therapy. Intrinsic ADCC was evaluated from ex vivo NK-dependent activity measuring LDH release through the Cytotox 96® non radioactive cytotoxicity assay, previously standardized in our laboratory (Crit Rev Oncol Hematol, 2015). EGFR tumoral expression was analyzed by immunohistochemistry. Results Median ADCC response at treatment start for all patients was 56.1% (range 5-99%). Analysing the whole population, patients with ADCC above the median value (high) showed a better OS as compared to patients with ADCC below the median (low), HR = 0.3827 (95% CI, 0.1464 to 1.000), p = 0.05 (Long-rank Mantel-Cox Test). A sub-group analysis confirmed a possible link between high ADCC and a better OS (CT-RT group, p = 0.223 and CT-RT+cetuximab group, p = 0.244). Importantly, considering CT-RT+cetuximab treatment and EGFR tumoral expression (N = 21), patients with EGFR 3+ status and high ADCC showed an improved OS as compared to patients with ADCC below median value, HR = 0.09031 (95% CI, 0.009983 to 0.8170), p = 0.032 (Long-rank Mantel-Cox Test). Median OS values for patients with high EGFR expression were 34.8 months (range 9.1-53.7) and 13.1 months (range 2.1-39.5) for patients with respectively high ADCC and low ADCC. Conclusion ADCC is shown to be a strong driver of cetuximab-based therapy outcome in HNSCC. High tumoral EGFR expression and high ADCC confer a particularly long overall survival. These data suggest an ADCC-based and EGFR expression-based precision therapy under cetuximab in HNSCC and open perspectives for NK boosting. Citation Format: Cristiana Lo Nigro, Laura Lattanzio, Daniela Vivenza, Martino Monteverde, Federica Tonissi, Giuliana Strola, Marco Merlano, Gerard Milano. Treatment outcome under cetuximab-based therapy and individual ADCC capability in head and neck cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1414.