Phase II trial of everolimus in patients with previously treated recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN).

Abstract

5541 Background: The PI3K/Akt/mTOR pathway plays an important role in SCCHN pathogenesis and resistance to treatment. We conducted a phase II study of everolimus, an oral inhibitor of mTOR, in patients with refractory SCCHN. Methods: Patients with recurrent or metastatic SCCHN treated with at least 1 prior regimen, performance status (PS) 0-2, and adequate organ function, received everolimus 10 mg once daily orally. The primary endpoint was the disease control rate (DCR) defined as the proportion of patients with a complete response, a partial response, or stable disease. A two-stage design was followed. Cytokines were measured in plasma and serum at baseline and post treatment. Results: 9 patients were enrolled. Median age 63 years (range 51 - 82), Male/Female, 6/3, performance status 0/1/2, 2/5/1. Primary site: oropharynx (2), oral cavity (4), larynx (1), others (2). Median number of palliative therapies in the recurrent/metastatic setting prior to study was 1 (range 1- 4). Median number of cycles of everolimus delivered was 1 (range 1-5). No objective responses were seen. One patient had stable disease that lasted 6 months but all other patients had progression as best response. DCR was 11%. Median progression-free survival was 40 days. Four patients have died due to disease progression. Grade 3 adverse events were infrequent: pain (2 patients), anemia (2 patients), and 1 patient each with pruritus, hypertransaminasemia, hyponatremia, lymphopenia, and fatigue. No Grade 4 toxicities were reported. Biomarker analysis in 2 patients with available post treatment samples showed reduced plasma levels of VEGF-A, Gro-α, and IL-17, after everolimus treatment, but no reduction was observed in the plasma levels of IL-6 and IL-8, two cytokines often associated with SCCHN disease progression. Conclusions: Everolimus as monotherapy was well tolerated but did not have sufficient activity in this setting. This phase II study did not meet the predefined primary endpoint in the first stage of accrual.