Immune-related saliva micro-RNA’s to predict clinical response to a combination of cetuximab and low-dose chemotherapy in head and neck cancer (HNSCC) patients (pts) with poor performance status (PS).

Abstract

e17548 Background: Recurrent/Metastatic HNSCC is an immunosuppressive disease, especially in the group of patients with poor performance status. Recent studies have shown that low dose chemotherapy, which is much better tolerated than full dose cytotoxic chemotherapy, can increase the anti-tumor immune response and cause tumor regression. In this study we assessed the immune-effects of weekly cetuximab in combination with low dose weekly chemotherapy in HNSCC pts with poor PS by measuring saliva and plasma immune modulatory micro RNAs (miRs). Methods: Patients with recurrent/metastatic HNC with an ECOG PS of 2 or 3 were treated with low-dose weekly carboplatin (AUC 1) and paclitaxel (25 mg/m2) along with weekly cetuximab (400mg/m2 followed by 250 mg/m2). Seven immune modulatory miRs (146a, 155, 181, 20a, 223, 335, 125b) were measured in the saliva and plasma by quantitative PCR prior to treatment and at week 5. Results: Between 4/2016 and 1/2017, 30 patients were enrolled in this study. 24 patients were evaluable for response. Mean age was 69 years (range 51-89), Male/Female: 14/8. ECOG PS 2/3: 13/9. Site of disease: oral cavity 7, pharynx 9, larynx 4, para-nasal 2, unknown 2. Treatment was well tolerated. The most common dose limiting toxicity was skin rash in 10/24 pts (41.5%). Response: partial response 12 (50%); stable disease 4 (16.5%); progressive disease 8 (33.5%). Reduction in miR levels by week 5 were associated with clinical response. Reduction in saliva levels of miRs 146a and 181 correlated with clinical benefit (PR+SD). Pre-treatment saliva levels of miR 146a also showed to be a predictor of tumor response to therapy. Plasma levels of the immune modulatory miRs tested were not associated with response to therapy. Conclusions: The combination of cetuximab and low-dose chemotherapy is active and well tolerated in HNSCC patients with poor PS. Reduction in saliva levels of immune modulatory miRs 146a and 181 were associated with clinical benefit to therapy.