Phase 2 Trial of Adjuvant Concurrent Cetuximab and Radiation for High-Risk Cutaneous Squamous Cell Carcinoma of the Head and Neck

Abstract

Aggressive cutaneous squamous cell carcinoma of the head and neck (CSCCHN) is most often treated with surgical resection followed by adjuvant radiation therapy (RT) with or without concurrent chemotherapy and locoregional control (LRC) remains problematic with 2 yr LRC of 60% to 80%. The addition of cytotoxic chemotherapy has not demonstrated benefit over adjuvant RT in randomized trials. NCT01979211 is a multi-institutional single arm phase 2 trial of concurrent adjuvant RT and cetuximab after primary surgical resection for CSCCHN. Eligibility criteria include high-risk (>N1, + PNI, bone or cartilage invasion) or locally recurrent CSCCHN after gross total resection. Primary endpoint is 2 yr LRC. Secondary endpoints include DFS, OS, acute and late toxicities (CTCAE v4.03), and patient reported quality of life with FACT-HN and Dermatology Life Quality Index (DLQI). Correlative studies include whole exome sequencing of primary tumor and nodal metastases. Twenty-three of planned 40 patients are accrued to date with a median 12 months of follow-up. Eighteen patients have completed all therapy per protocol with minimum 3-month follow-up. Of the patients, 91% were male, mean age 69 (range 50-80), all Zubrod 0-1. Of these, 18 patients, acute toxicities are as follows: 91% had grade 1 toxicities, mostly acneiform rash and mucositis, grade 2 reported in 61% patients including skin (39%), mucositis/oral pain (39%), fatigue (11%), allergic reaction (5%). Three patients had grade 3 skin toxicity, 1 patient had grade 3 mucositis. No grade 4 or 5 toxicities to date. Two patients developed locoregional failures, no one has developed distant metastases. 2 patients have died, 1 related to confirmed LRR. To date, mean baseline DLQI score is 5.5 (+/- 0.5) and at 3 mo post-RT is 3.9 (+/- 0.4), indicating a “small” improvement in skin QOL from postresection, preadjuvant therapy baseline. Mean baseline FACT- HN score is 120 (+/- 18) and 118 (+/- 25) at 3 mo post-RT. Postoperative concurrent cetuximab and RT for high risk CSCCHN appears well tolerated with favorable LRC thus far in comparison to institutional historic controls and quality of life scores comparable to other trials using concurrent cetuximab and RT for mucosal HNSCC.