Zosia Chustecka

May 12, 2011

May 12, 2011 (London, United Kingdom) — The hottest topic in head and neck cancers is the role of human papillomavirus (HPV) in the disease, although there is also a lot interest in treatment with EGFR inhibitors, especially the second-generation products, according to an expert here at the European Society for Therapeutic Radiology and Oncology 11th Biennial Conference.

HPV has only been associated with head and neck cancer in the last few years, but it is now clear that patients who are positive for the virus have a better prognosis, said Cai Grau, MD, DMSC, professor of oncology at Aarhus University Hospital, Denmark. He chaired a session during which both hot topics were discussed.

"These patients have a better prognosis, irrespective of treatment, and their risk of a second cancer is virtually zero," added session participant Lisa Licitra, MD, medical oncologist at the Istituto Nazionale per lo Studio e la Cura dei Tumori in Milan, Italy.

However, there is a difference between patients in the United States and those in Europe with regard to risk, she told meeting attendees.

For American patterns, Dr. Licitra cited the analysis published last year in the New England Journal of Medicine (2010;363:24-35), which reported a risk model for death from oropharyngeal squamous cell carcinoma on the basis of HPV status, pack-years of tobacco smoking, and tumor and nodal stage. In this 266-patient cohort, 43% were low risk, 30% were intermediate risk, and 27% were high risk.

Dr. Licitra reported that when she performed the same analysis on a cohort of 120 patients at her institution, the percentages were different — among the Italian patients, 22% were low risk, 38% were intermediate risk, and 40% were high risk.

"There were more high-risk and fewer low-risk patients," she pointed out, and speculated in an interview that this might be because of higher rates of smoking in Italy.

These differences in risk estimates might account for differences in outcomes between European and American patients in international trials of head and neck cancer, Dr. Licitra said. For instance, this was seen in a trial by Bonner et al (N Engl J Med. 2006:354;567-578), which showed that the EGFR inhibitor cetuximab (Erbitux) added to radiotherapy was an effective option in head and neck cancer.

Dr. Lisa Licitra

The European patients in the Bonner trial fared worse than the American patients, and there has been a lot of speculation as to why, she noted in an interview.

There were suggestions that radiotherapy improved outcomes in the United States, for example. But the new data reported by Dr. Licitra suggest another potential explanation: the European patients might have had worse outcomes because more were negative for HPV and at higher risk for recurrence. "We now appreciate that the patient population is different," she explained.

However, she emphasized that this is speculation; the participants of the Bonner trial were not tested for HPV status.

Going forward, clinical trials of patients with head and neck cancer are now stratifying for HPV status, Dr. Licitra and Dr. Grau both noted.

Less Intense Therapy?

One of the issues being explored is whether the management should be different for head and neck cancer patients who are positive for HPV. There is a suggestion that, because of their better prognosis, these patients could undergo less intense therapy.

However, so far "the scientific evidence for this is not strong," Kevin Harrington, FRCP, FRCR PhD, senior lecturer at the Institute of Cancer Research, and honorary consultant oncologist at the Royal Marsden Hospital, London, United Kingdom, told meeting attendees.

Standard treatment for head and neck cancer is chemoradiation, which is supported by level 1a evidence from controlled randomized clinical trials, he noted. The gold standard is single-agent cisplatin with radiotherapy.

There are data that show that HPV-positive patients have a significantly better outcome than HPV-negative patients, deriving about 35% greater benefit, he said. "But it is difficult to suggest abandoning chemoradiation," he said. There might be a case for replacing cisplatin with a less toxic chemotherapeutic and/or deescalating the radiation dose, he added.

EGFR inhibitors such as cetuximab offer another therapy option. Clinical trials so far have added cetuximab to radiotherapy (as the Bonner trial did) and added cetuximab to chemoradiotherapy. This option is attractive because these drugs are oral and less toxic than chemotherapy such as cisplatin. As a result, there has been a separate trend within head and neck cancer to assess tumors for EGFR-receptor expression.

Initially, there was hope that the patients with HPV-positive tumors, who have a better prognosis, would be the patients who would respond best to treatment with EGFR inhibitors, and thus avoid chemotherapy, Dr. Grau explained.

However, there appears to be little interaction between HPV and EGFR inhibitors, Dr. Harrington said. "We were looking to see if HPV and EGFR are talking to one another," he said, but "there is no evidence in the medical literature that they are interacting at a molecular or mechanistic level."

The data do not support the notion that patients who have HPV-positive tumors are good candidates for treatment with EGFR inhibitors, he said.

Currently, chemoradiation with single-agent cisplatin remains the gold standard treatment for head and neck cancer. This is the treatment against which all new options will be measured, Dr. Harrington noted.

An ongoing trial (NCT00820248) is the first head-to-head trial to test the standard treatment of cisplatin with radiotherapy against a newer option — radiotherapy combined with the second-generation EGFR inhibitor panitumumab, he said.

European Society for Therapeutic Radiology and Oncology (ESTRO) 11th Biennial Conference: Abstracts 59 and 61. Presented May 9, 2011.


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