In the phase III De-ESCALaTE trial reported in The Lancet, Mehanna et al found no difference in severe toxicity with cisplatin vs cetuximab (Erbitux) plus radiotherapy in low-risk human papillomavirus (HPV)-positive oropharyngeal cancer. Cetuximab was associated with poorer recurrence and survival outcomes.
In the open-label trial, 334 patients with HPV-positive low-risk oropharyngeal cancer (nonsmokers or lifetime smokers with a smoking history of < 10 pack-years) from 32 sites in Ireland, the Netherlands, and the United Kingdom were randomly assigned between November 2012 and October 2016 to receive radiotherapy at 70 Gy in 35 fractions, plus either intravenous (IV) cisplatin at 100 mg/m² on days 1, 22, and 43 of radiotherapy (n = 166) or IV cetuximab at a 400 mg/m² loading dose followed by 7 weekly infusions of 250 mg/m² (n = 168).
The aim of the trial was to determine whether the cetuximab strategy could reduce the toxicity associated with standard cisplatin treatment. The primary outcome measure was overall acute and late grade 3 to 5 toxicity at 24 months from the end of treatment.
Severe and All-Grade Toxicity
Median follow up was 25.9 months. In intent-to-treat analysis at 24 months, the mean number of acute and late severe adverse events per patient was 4.8 in the cisplatin group vs 4.8 in the cetuximab group (P = .98). The mean number per patient of any-grade events was 29.2 vs 30.1 (P = .49).
In the acute period, there was no difference in severe toxicity (mean = 4.4 vs 4.4 events per patient, P = .84) or any-grade toxicity (mean = 20.0 vs 20.4 events per patient, P = .64). No difference was observed in late severe toxicity (mean = 0.4 vs 0.5 events per patient, P = .53) or late any-grade toxicity (mean = 9.4 vs 9.9 events per patient, P = .49). Similar results were found in the per-protocol population.
Recurrence and Survival Rates
Two-year overall survival was 97.5% in the cisplatin group vs 89.4% in the cetuximab group (hazard ratio [HR] = 5.0, P = .001) and 2-year recurrence rates were 6.0% vs 16.1% (HR = 3.4, P = .0007). It was estimated that the use of cetuximab instead of cisplatin was associated with 1 extra death at 2 years for every 12 patients treated.
The investigators concluded, “Compared with the standard cisplatin regimen, cetuximab showed no benefit in terms of reduced toxicity, but instead showed significant detriment in terms of tumor control. Cisplatin and radiotherapy should be used as the standard of care for HPV-positive, low-risk patients who are able to tolerate cisplatin.”
Hisham Mehanna, PhD, of the Institute of Head and Neck Studies and Education, University of Birmingham, is the corresponding author for The Lancet article.
Disclosure: The study was funded by Cancer Research UK. See the study authors’ full disclosures at thelancet.com.
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