Adjuvant Chemoradiation With Docetaxel Plus Cetuximab Shows Promise in High-Risk Squamous Cell Carcinoma of the Head and Neck
In the phase II Radiation Therapy Oncology Group (RTOG)-0234 trial reported in the Journal of Clinical Oncology, Harari et al found that adjuvant chemoradiation with docetaxel or cisplatin plus cetuximab (Erbitux) in patients with squamous cell carcinoma of the head and neck and high-risk pathologic features produced outcomes that compare favorably with historical controls not receiving cetuximab. Outcomes were better in patients in the docetaxel group, and the chemoradiation regimen with docetaxel plus cetuximab has been advanced to phase II/III study.
Study Details
In the study, 203 patients with pathologic stage III to IV squamous cell carcinoma of the head and neck with gross total resection showing positive margins or extracapsular nodal extension or at least two nodal metastases were randomly assigned between April 2004 and December 2006 to 60 Gy radiation with cetuximab once per week plus either cisplatin at 30 mg/m2 (n = 97) or docetaxel at 15 mg/m2 (n = 106) once per week. Cetuximab was started 5 to 9 days before radiation at a loading dose of 400 mg/m2 followed by six weekly infusions of 250 mg/m2 during radiation.
The cisplatin and docetaxel groups were generally balanced for age (median, 57 and 56 years), sex (79% and 70% male), Zubrod performance status (0 in 50% and 51%, 1 in 50% and 49%), primary site (eg, oral cavity in 46% and 47%, oropharynx in 39% and 34%), pathologic T stage (T1 in 20% and 24%, T2 in 34% and 30%,T3 in 14% and 21%, T4 in 32% and 26%), pathologic N stage (eg, N2b in 58% and 64%, N2c in 23% and 17%), pathologic American Joint Committee on Cancer stage (eg, IV in 94% and 93%), positive margins (42% and 40%), extracapsular nodal extension (60% and 59%), at least two pathologically positive nodes (85% and 84%), and planned intensity-modulated radiation therapy (37% and 40%).
Disease-Free and Overall Survival
Median follow-up was 4.4 years. Two-year overall survival was 69% in the cisplatin group and 79% in the docetaxel group, and 2-year disease-free survival was 57% and 66%. Outcomes were better in patients with p16-positive vs p16-negative oropharynx cancer in both the cisplatin group (2-year overall survival = 90.9% vs 40.0%, hazard ratio [HR] = 0.13, P = .002) and the docetaxel group (100.0% vs 66.7%, HR = 0.14, P = .003). For the cisplatin vs docetaxel groups, first site of failure was locoregional in 39.6% vs 43.1%, distant in 37.5% vs 19.6%, second primary in 8.3% vs 23.5%, and death in 14.6% vs 13.7%.
Comparison vs Historical Controls
Comparison of disease-free survival with that in the patients receiving adjuvant radiation and cisplatin in the phase III RTOG-9501 trial showed improved outcomes with cisplatin/cetuximab (HR = 0.76, P = .05) and docetaxel/cetuximab (HR = 0.69, P = .01), reflecting absolute improvements in 2-year disease-free survival of 2.5% and 11.1%. Similarly, 2-year overall survival was improved with cisplatin/cetuximab (HR = 0.72, P = .04) and docetaxel (HR = 0.56, P = .001) compared with the historical controls.
Adverse Events
For the cisplatin and docetaxel groups, the most common grade 3 or 4 nonhematologic adverse events were mucositis (56% vs 54%), dysphagia (38% vs 37%), and skin rash (36% vs 39%). Grade 3 or 4 hematologic toxicity was more common in cisplatin patients (28% vs 14%). The most common grade 3 late toxicity was dysphagia (6.0% vs 3.2%).
The investigators concluded, “The delivery of postoperative chemoradiotherapy and cetuximab to patients with [squamous cell carcinoma of the head and neck] is feasible and tolerated with predictable toxicity. The docetaxel regimen shows favorable outcome with improved [disease-free survival] and [overall survival] relative to historical controls and has commenced formal testing in a phase II/III trial.”
Paul M. Harari, MD, of University of Wisconsin School of Medicine and Public Health, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by grants from the Radiation Therapy Oncology and National Cancer Institute and by Bristol-Myers Squibb and sanofi-aventis. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
