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SCOTTSDALE, Ariz. -- Chemoradiation plus a targeted agent failed to improve disease control or survival in patients with squamous cell head and neck cancer as compared with chemoradiation alone, a randomized trial showed.

The 3-year rates of locoregional control were 77% with chemoradiation and 76% with chemoradiation plus zalutumumab, an inhibitor of epidermal growth factor receptor (EGFR). Disease-specific survival (DSS) and overall survival (OS), secondary endpoints, also did not differ significantly between groups but were higher in the control group.

Investigators found no patient subgroups that fared better with the antibody than without it, including human papillomavirus (HPV) status, , reported here at the Multidisciplinary Head and Neck Cancer Symposium (MHNCS).

"If anything, there is a slight tendency that zalutumumab is doing [not as well as] the control arm," said Overgaard, of Aarhus University Hospital in Denmark.

Several other presentations attracted interest at MHNCS, including a study on the impact of concurrent chemoradiation on survival in squamous cell head and neck cancer, and the effect of HPV status on disease prognosis.

Zalutumumab Disappoints

Overgaard reported the negative outcomes from a randomized trial involving 619 patients with biopsy-proven squamous-cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. Almost 90% of the patients had stage III-IV disease.

All patients received curative radiation therapy with the radiosensitizer nimorazole, and those with stage III-IV disease also received concurrent cisplatin. They were randomized to zalutumumab or no additional treatment.

The primary endpoint was locoregional control. After a median follow-up of 36 months, investigators found no difference between treatment groups with respect to the primary endpoint. DSS was 85% in the control group and 82% in the zalutumumab arm, and analysis of OS showed a larger difference in favor of the control group (79% versus 72%).

Overgaard reported that 94% of patients in the zalutumumab group developed a skin rash, which was grade 3/4 in severity in 29% of patients. Additionally, 11% of zalutumumab-treated patients discontinued because of the rash.

The results are consistent with those of the trial, which showed no advantage of adding cetuximab (Erbitux) to chemoradiation for patients with squamous cell head and neck cancer, said , of the University of Wisconsin in Madison, who was an invited discussant.

On the other hand, the landmark EXTREME trial established chemoradiation plus cetuximab as an effective therapy for patients with metastatic and recurrent head and neck cancer.

"Where we have a lot of unanswered questions is in acknowledging how little we actually understand about EGFR biology, despite 40 years of progressive knowledge," Harari said.

Chemoradiation Tops Accelerated RT

Concurrent chemoradiation led to significantly better survival compared with accelerated radiation therapy in patients with "moderately advanced" head and neck cancer, Polish investigators reported.

After a median follow-up of 30 months, patients treated with chemoradiation had an actuarial 2-year survival of 81% compared with 62% for patients who received accelerated radiation therapy. Disease-free survival (DFS) was 75% and 62%, respectively, for chemoradiation and accelerated radiotherapy.

Meta-analyses have suggested that patients who derive the most benefit from chemoradiation have advanced disease (T3-4, N2-3). As a result, accelerated radiation therapy has been considered an acceptable standard for patients with less advanced head and neck cancer, said , of Curie Memorial Cancer Center in Gliwice, Poland.

To examine the efficacy of accelerated radiotherapy in less advanced disease, investigators enrolled 101 patients with T2 N1-2 to T4A N0-2 squamous cell head and neck cancer. Patients were randomized to accelerated radiation therapy (72 Gy, 40 fractions in 40 days) or to radiation therapy (70 Gy, 35 fractions in 49 days) plus cisplatin. Intensity-modulated radiation therapy was used in all cases.

The survival advantage for chemoradiation accrued from lower rates of primary and neck failures, distant metastasis, and deaths, Skladowski said.

In the subgroup of patients with known HPV status (11 HPV-positive, 35 HPV-negative), the two treatment strategies have led to similar outcomes in HPV-positive patients, all of whom remain alive. The HPV-negative patients had a 2-year survival of 80% with chemoradiation and 60% with accelerated radiotherapy.

HPV Effect on Prognosis Persists in Recurrence

Patients with progressive or recurrent HPV-positive oropharyngeal cancer had a 2-year overall survival twice that of patients with HPV-negative cancer, combined data from two cooperative-group trials showed.

The 105 HPV-positive patients had a 2-year survival of 54.6% versus 27.6% for patients with HPV-negative cancer. The survival disparity persisted in patients who had salvage surgery and those who did not, although surgery improved survival regardless of HPV status, reported , of Johns Hopkins University in Baltimore.

HPV infection accounts for a majority of all newly diagnosed head and neck squamous cell carcinoma. Newly diagnosed HPV-positive head and neck cancer has a more favorable prognosis as compared with HPV-negative cancers, including survival. Whether the prognostic significance of HPV status persisted in advanced disease had not been studied extensively.

Fakhry and colleagues identified 181 patients with known HPV status from databases of the Radiation Therapy Oncology Group 0129 and 0522 trials. Time to recurrence did not differ between HPV-positive (8.2 months) and HPV-negative (7.3 months) patients.

Using p16 immunohistochemistry as a surrogate for HPV status, investigators found that p16+ patients had significantly better survival after recurrence (P<0.001). In the subset of patients who had salvage surgery, 2-year survival was 72.4% for patients with p16+ tumors versus 45% for patients with p16- tumors (P=0.004).

Among patients who did not undergo salvage surgery, 2-year overall survival was 47.4% for p16+ patients and 20.9% for p16- patients (P=0.003).