Systemic Therapy Wins One, Loses One in Head and Neck Cancer

Charles Bankhead

March 2014, Vol 5, No 2 - Head and Neck Cancer


Scottsdale, AZ—The addition of chemotherapy to irradiation proved superior to accelerated radiotherapy without systemic therapy in a randomized trial of patients with advanced head and neck cancer.

Chemoradiation led to better overall survival (OS) at 2 years and to improved disease-free survival (DFS) in patients with mid-level disease status. Among patients whose human papillomavirus (HPV) status was known, chemotherapy improved 2-year survival by more than 30% in the HPV-negative subgroup, which had a less favorable prognosis, according to a report presented at the 2014 Multidisciplinary Head and Neck Cancer Symposium.

“Early results of the Polish HN08 trial have proven that concurrent chemoradiation takes an advantage over accelerated radiotherapy in patients with marginally advanced head and neck squamous-cell carcinoma,” said Krzysztof Skladowski, MD, PhD, Head of Radiation Oncology, Institute of Oncology–Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland.

“For these patients, concurrent chemoradiation with conventional 7 weeks of fractionation and, at least, 2 courses of cisplatin is more effective than 6 weeks of accelerated radiation therapy. Perhaps the target for accelerated radiation therapy could be now limited for the population of patients with T2 head and neck squamous-cell carcinoma or to HPV-positive oropharyngeal cancer patients.”

Another study reported at the meeting showed that the addition of an epidermal growth factor receptor (EGFR) inhibitor to chemoradiation did not significantly improve locoregional control compared with chemoradiation and placebo.

Several meta-analyses have suggested that patients with advanced head and neck cancer derive the most benefit from concurrent chemoradiation. As a result, accelerated radiotherapy without chemotherapy has been considered an acceptable standard for patients with less advanced disease, said Dr Skladowski. However, the 2 strategies had not been compared directly in a randomized trial involving patients with less advanced forms of head and neck cancer.

Investigators at the Gliwice cancer center enrolled 101 patients with T2N1-2 to T4AN0-2 squamous-cell head and neck cancer. Patients received accelerated radiation therapy at a dose of 72 Gy delivered in 40 fractions over 40 days, or radiation therapy at a dose of 70 Gy in 35 fractions over 49 days plus cisplatin 100 mg/m2 on days 1, 22, and 43.

After a median follow-up of 30 months, the chemoradiation group had a 2-year survival of 81% versus 62% for the patients who received accelerated radiotherapy (P = .02). DFS was 75% with chemoradiation and 60% with accelerated radiation therapy (P = .05).

The patients treated with radiation therapy alone had a primary failure rate of 23% compared with 14% for the chemoradiation arm. The patients treated with accelerated radiation therapy also had higher rates of neck failure and distant metastasis.

Overall, HPV status was known in 46 patients. The 2-year survival in 11 patients with HPV-positive cancer was similar with either treatment. In 35 patients with HPV-negative cancer, 2-year survival was 80% with chemoradiation and 60% with accelerated radiation therapy.

Investigators in a multicenter Scandinavian trial found that adding the EGFR inhibitor zalutumumab to chemoradiation did not improve 3-year locoregional control compared with chemoradiation therapy by itself. OS and disease-specific survival also did not differ significantly between the groups, but were nu­merically higher in the chemoradiation group.

“If anything, there was a slight tendency for the zalutumumab group to do not as well as the control arm,” said Jens Overgaard, MD, DMSc, Professor of Clinical Medicine and of Experimental Clinical Oncology, Aarhus University Hospital, Denmark.

Investigators in Denmark and Norway enrolled 619 patients with squamous-cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. All patients received accelerated radiation therapy (66-68 Gy, 2 Gy/fraction, over 6 weeks) plus the radiosensitizer nimorazole. All patients (89%) with stage III to IV disease also received concurrent weekly cisplatin 40 mg/m2. The patients were randomized to receive zalutumumab or no additional therapy.

The primary end point was locoregional control. After a median follow-up of 36 months, the 3-year locoregional control rates were 77% in the control arm and 76% in the zalu­tumumab group. Disease-specific survival (85% vs 82%) and OS (79% vs 72%) also favored the control arm.

“We found no patient subgroup that seemed to do better with zalutumu­mab, including HPV status,” said Dr Overgaard.