Linda Brookes, MSc


October 17, 2013

In This Article

Update on Treatment Strategies

Concomitant chemoradiotherapy remains the standard of care for patients with locally advanced head and neck squamous cell carcinomas. New data presented by Dr. Lassen showed "significant benefit" in patients with HPV/p16-positive oropharyngeal carcinoma stage III-IV, treated with what is the standard in Denmark: accelerated radiotherapy (66-68 Gy, 2 Gy/F, 6 F/week) plus nimorazole 1200 mg/m2, plus cisplatin 40 mg/m2 once weekly.[7]

Nimorazole (Nimoral) is a hypoxic radiosensitizer that has been used in routine clinical practice in Denmark and Norway for more than 20 years. It received orphan designation from the European Medicines Agency (EMA) in 2011 for the treatment of head and neck cancer and has recently become available, in compassionate-use programs, in other European countries, including the United Kingdom, Belgium, and The Netherlands.

In the DAHANCA 18 study, locoregional control with chemoradiotherapy at 5 years was 88% in HPV/p16-positive patients compared with 66% in HPV/p16-negative patients (P = .006) and there was an "impressive" overall survival rate of 93% vs 63%, respectively (P < .0001), reported Dr. Lassen.[7] She described how this result was confirmed in a retrospective analysis of data from over 1400 patients with stage III-IV oropharyngeal cancer who were treated with the same regimen in DAHANCA phase 3 trials (88% vs 76% locoregional control at 5 years). Nonetheless, "the outcome of 76% in the HPV/p16-negative patients was actually quite good when compared with what else has been reported," she noted.

On the basis of these results, an international collaborative study (1219 ROG-HNCG) is being initiated by DAHANCA and the European Organisation for Research and Treatment of Cancer (EORTC) to investigate whether the addition of nimorazole to concomitant radiotherapy and cisplatin improves outcome in HPV/p16-negative patients. The trial will also examine whether using a 15-gene profile for hypoxia will be able to predict which patients will benefit from the addition of nimorazole. In speaking with Medscape, Dr. Lassen stressed, "Patients with HPV-negative tumors have a poor prognosis, and efforts should be made to optimize outcome in this group of patients."

Less is known about chemotherapy with other radiosensitizers in HPV-positive oropharyngeal cancer. The RTOG 0129 study showed no difference between accelerated fractionated radiotherapy vs standard fractionated radiotherapy, each combined with cisplatin overall, and it is not yet known from this trial whether either treatment is beneficial in HPV subgroups.[8] Significant survival benefit was seen in head and neck cancer patients with radiotherapy plus the epidermal growth factor receptor (EGFR) inhibitor cetuximab vs radiotherapy alone.[9] No viral analysis was done in this study, but the greatest benefit from cetuximab was seen in patients likely to have HPV/p16-positive tumors (namely in younger, fitter patients who had oropharyngeal primary tumors, of smaller size, and who had large lymph node involvement.)[10]

As reported in Amsterdam, the first results of the DAHANCA 19 phase 3 trial showed that addition of the EGFR inhibitor zalutumumab to primary chemoradiotherapy plus nimorazole did not produce any benefit over primary chemoradiotherapy and nimorazole for the treatment of head and neck cancer, with no improvement in locoregional control or disease-specific or overall survival at 3 years.[11] No viral data were presented, but additional analyses are under way.

Another issue that remains unresolved is the treatment of patients with non-oropharyngeal HPV/p16-positive tumors. "They are outnumbered by the oropharyngeal cases, but we need to look further into them," Dr. Lassen told Medscape.