In the Swedish ARTSCAN III trial reported in the Journal of Clinical Oncology, Gebre-Medhin et al found that radiotherapy with concomitant cetuximab did not improve outcomes vs radiotherapy with cisplatin in patients with previously untreated, locoregionally advanced head and neck squamous cell carcinoma.
Study Details
In the phase III, open-label, multicenter trial, 291 patients (intent-to-treat population) were randomly assigned between November 2013 and March 2018 to receive radiotherapy plus cisplatin (n = 145) or radiotherapy plus cetuximab (n = 146). Treatment consisted of weekly cisplatin at 40 mg/m2 or cetuximab at 400 mg/m2 1 week before start of radiotherapy followed by 250 mg/m2 per week during radiotherapy.
Radiotherapy was conventionally fractionated. Patients with T3 or T4 tumors underwent a second random assignment between a standard radiotherapy dose of 68.0 Gy to the primary tumor or dose escalation to 73.1 Gy.
The primary endpoint was overall survival. Analysis was adjusted for tumor site, T stage/dose escalation, and performance status.
Treatment Outcomes
Study inclusion was prematurely closed after an unplanned interim analysis in 2018, with the recommendation to terminate enrollment based primarily on a clear difference in locoregional events (12 in the cisplatin group vs 28 in the cetuximab group). At the time of analysis, median follow-up was 38 months in the cisplatin group and 39 months in the cetuximab group.
At 3 years, overall survival was 78% in the cetuximab group vs 88% in the cisplatin group (adjusted hazard ratio [HR] = 1.63, 95% confidence interval [CI] = 0.93–2.86; P = .086).
KEY POINTS
- Study enrollment was stopped early.
- Radiotherapy with cisplatin was associated with significantly reduced locoregional recurrence vs radiotherapy with cetuximab.
The cumulative incidence of locoregional failures at 3 years was 23% in the cetuximab group vs 9% in the cisplatin group (P = .0036; adjusted cause-specific HR = 2.49, P = .0045). The cumulative incidence of distant failures at 3 years was 9% in the cetuximab group vs 6% in the cisplatin group (P = .52; adjusted cause-specific HR = 1.45, P = .39).
Event-free survival at 3 years was 67% vs 85% (P = .0054; adjusted HR = 1.99, P = .0053). No significant difference in local control was observed between patients who received dose escalation to 73.1 Gy vs those receiving the standard radiotherapy dose.
Toxicity
Acute toxicity profiles differed between groups; nausea, vomiting, acute kidney injury, neutropenia, tinnitus, and dysphagia were significantly more common in the cisplatin group, and mucositis, skin reactions, and acneiform rash were significantly more common in the cetuximab group. Among late adverse events, pain and poor oral mucosa status was significantly more common in the cetuximab group, and taste alteration and hearing impairment were significantly more common in the cisplatin group.
The investigators concluded, “Cetuximab is inferior to cisplatin regarding locoregional control for concomitant treatment with radiotherapy in patients with locoregionally advanced head and neck squamous cell carcinoma. Additional studies are needed to identify possible subgroups that still may benefit from concomitant cetuximab treatment.”
Maria Gebre-Medhin, MD, of the Department of Hematology, Oncology, and Radiation Physics, Skåne University Hospital, Lund University, Lund, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Swedish Cancer Society and the Mrs. Berta Kamprad Cancer Foundation. For full disclosures of the study authors, visit ascopubs.org.
