Addition of Concurrent Chemotherapy to EGFR Inhibitor and Radiotherapy in Locally Advanced Head and Neck Carcinoma
As reported in the Journal of Clinical Oncology by Tao et al, the phase III GORTEC (Groupe Oncologie Radiothèrapie Tête et Cou) 2007-01 trial has shown improved progression-free survival with the addition of concurrent chemotherapy to cetuximab (Erbitux) and radiotherapy (RT) in locally advanced head and neck squamous cell carcinoma.
Study Details
In the open-label trial, 406 patients from 31 centers were randomized between January 2008 and March 2014 to receive RT up to 70 Gy (2 Gy per fraction 5 days a week) with weekly cetuximab (n = 202; loading dose of 400 mg/m2 on day 7 followed by a weekly dose of 250 mg/m2 during RT) or with weekly cetuximab and concurrent chemotherapy (n = 404) consisting of carboplatin (70 mg/m2 on days 1–4) and fluorouracil (600 mg/m2 on days 1–4) for 3 cycles. All patients had squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx with N0–2b, nonresected stage III or IV (nonmetastatic) disease.
The primary endpoint was progression-free survival. More than 60% of patients in both groups had oropharyngeal carcinoma, and 79% in both groups were p16 negative.
Efficacy Outcomes
Median follow-up was 4.4 years. Progression-free survival at 3 years was 52.3% in the concurrent chemotherapy group vs 40.5% in the control group, and median progression-free survival was 37.9 vs 22.4 months (hazard ratio [HR] = 0.73, P = .015). The cumulative incidence of locoregional failure was 21.6% vs 38.8% (HR = 0.54, P < .001). Overall survival at 3 years was 60.8% vs 54.9% (HR = 0.80, P = .11; median = 53.4 vs 44.5 months). No difference between groups was observed in rate of distant metastases considered as a first event (HR = 1.19, P = .50). Among patients with oropharyngeal carcinoma, a progression-free survival benefit of concurrent chemotherapy was observed among those with p16-negative (HR = 0.63, 95% confidence interval [CI] = 0.44–0.91) and p16-positive disease (HR = 0.23, 95% CI = 0.07–0.73).
Toxicity
The concurrent chemotherapy group had a higher incidence of grade 3 or 4 mucositis (73% vs 61%, P = .014), hospitalizations for toxicity (42% vs 22%, P < .001), and use of a feeding tube (67% vs 54%, P = .01). Death during or up to 30 days after completion of treatment occurred in 10 vs 3 patients.
The investigators concluded, “The addition of concurrent carboplatin and fluorouracil to [cetuximab and RT] improved [progression-free survival] and locoregional control, with a nonsignificant gain in survival. To our knowledge, this is the first evidence of a clinical benefit for treatment intensification using [cetuximab and RT] as a backbone in [locally advanced squamous cell carcinoma of the head and neck].”
The study was supported by Merck Serono (France), an affiliate of Merck KGaA (Darmstadt, Germany).
Jean Bourhis, MD, PhD, of Centre Hospitalier Universitaire Vaudois, Lausanne, is the corresponding author for the Journal of Clinical Oncology article.
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