Carboplatin (C), cetuximab (Cet), and everolimus (E) in recurrent or metastatic squamous cell carcinoma of the head and neck (RMSCCHN). Results of a phase Ib study

6083 Background: Platinum-based therapy in combination with Cet is the standard first line systemic therapy in RMSCCHN. Preclinical studies suggest that mTOR inhibitors may restore sensitivity to EGFR inhibitors in resistant cell lines, and that in combination with Cet may augment anti-tumor activity. We conducted a phase Ib trial of C, Cet and E for untreated RMSCCHN. Methods: Patients received C at AUC=2 on a 3 weeks on 1 off schedule with Cet weekly at a fixed dose and E at escalating dose levels of 2.5, 5.0, 7.5 and 10 mg daily using a 3+3 design. After 4 cycles of therapy patients without disease progression continued on maintenance Cet and E until disease progression or intolerable toxicity. Patients had previously untreated RMSCCHN not amenable to surgery or radiotherapy, age ≥ 18 years and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2. Results: After IRB approval, the study enrolled 18 patients with RMSCCHN between February 8, 2011 and Jan 25 2013. One patient was a screen failure. Four had an anaphylactic reaction to Cet and were excluded from the analysis. A total of 13 patients received E (M/F: 92%); median age 65 (44-75yrs). Two of six patients treated at dose level 1 (E-2.5 mg/day) experienced dose limiting toxicity (DLT) with grade 3 hyponatremia and nausea. Additional 7 patients were treated with de-escalated dose of E (2.5 mg QOD). No DLTs were observed at this dose level. Salient clinically relevant Grade >2 toxicities included: leukopenia (23%), neutropenia (15%) hyponatremia (18%), hyperglycemia, nausea, rash, hypokalemia, urinary infection, bacteremia, (each 8%). Dose reductions of C were necessary for a total of 18/61 delivered cycles of therapy. A response rate (RR) of 62.5% with all responders having partial responses (PR) was observed. The PFS was 7.8 months. Conclusions: The MTD of E in combination with Cet and C is estimated at 2.5 mg QOD. Though this is less than the commonly utilized dose of E, the regimen was associated with encouraging response rate and PFS Clinical trial information: NCT01283334.