Abstract C166: Phase II study of cetuximab and lenalidomide in recurrent/metastatic squamous cell carcinoma of the head and neck.

Background: IgG1 antibodies can activate immune responses including antibody dependent cellular cytotoxicity (ADCC), which can be an important facet of their efficacy. We hypothesized that FcγRIIIa polymorphic (valine/phenylalanine at position 158) genotype in the presence of lenalidomide would be associated with enhanced immune and clinical response of cetuximab, an IgG1 anti-EGFR antibody, in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). We evaluated patient9s FcγRIIIa polymorphic genotype and their ex-vivo Natural Killer cell (NK) activity with an ADCC assay to determine whether there was a correlation between FcγRIIIa genotype and NK activity with clinical outcome in subjects treated with cetuximab and lenalidomide. Materials and Methods: We conducted a multi-institutional phase II study involving patients with recurrent or metastatic SCCHN who were treated w[[Unable to Display Character: i]]th cetuximab (500 mg/m2 IV every 2 weeks) and lenalidomide (25 mg orally or via feeding tube once daily). In addition to determining patients FcγRIIIa polymorphism, we studied the activity of patient9s NK cells ex-vivo to determine how effectively their NK cells could mediate ADCC against SCCHN cell line TU167 in the presence of cetuximab. Finally, subjects receiving cetuximab and lenalidomide were followed for progression-free survival (PFS) and overall survival (OS). Results: We enrolled 42 patients (32 male, 10 female, mean age 61 years) with recurrent or metastatic SCCHN from three tertiary care centers: University of Chicago, University of Maryland, and Medical College of Wisconsin. Mean duration of therapy was 12 weeks with median PFS and OS of 7.2 and 16.4 weeks, respectively. Determination of patients FcγRIIIa polymorphic genotype at position 158 was available for 36 patients: V/V 2, F/V 20, and F/F 14. Twenty-six patients had adequate harvest of NK cells to perform ex vivo ADCC. While FcγRIIIa polymorphic genotype was not associated with clinical outcomes, patients who demonstrated elevated ex-vivo ADCC compared to patients who did not, showed a trend toward increased PFS, 14 vs 6.8 weeks, respectively p=0.12. Additionally, patients who were HPV+ demonstrated a trend toward increased OS, hazard ratio of 0.3 vs 1.0, respectively p=0.09. Conclusions: This is a challenging patient population with a substantial burden of oncologic disease having failed definitive standard of care treatment as well as other palliative modalities, culminating in reduced potency of their overall immune response. Treatment with combination cetuximab and lenalidomide in patients with recurrent or metastatic SCCHN was feasible. For patients who have NK that can still mount an ex-vivo ADCC response, they may experience longer PFS. Patients who are HPV+ may also encounter better OS. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C166. Citation Format: Rodney J. Taylor, Vassiliki Saloura, Richard Wong, Olga Goloubeva, Lorna Silpino, Jonas de Souza, Tanguy Seiwert, Everett Vokes, Ezra Cohen, Victoria Villaflor. Phase II study of cetuximab and lenalidomide in recurrent/metastatic squamous cell carcinoma of the head and neck. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C166.