In the Pipeline: Nimotuzumab Active in Head and Neck Cancer

Elsevier Global Medical News. 2009 Nov 6, P Wendling

CHICAGO (EGMN) - Nimotuzumab in combination with radiation and chemoradiation appears to offer an extended survival benefit in advanced head and neck cancer without severe, class-associated toxicities, according to long-term data from the BEST trial.

A monoclonal antibody targeting the epidermal growth factor receptor (EGFR), the novel agent is in late-stage development in the United States and Canada for a variety of cancers.

The four-arm, phase IIb open-label study randomized 92 patients with inoperable, stage III/IVa head and neck cancer to radiation alone (RT), chemoradiation (CRT) alone, RT plus nimotuzumab, or CRT plus nimotuzumab.

At 48 months, overall survival was 52% in the nimotuzumab-plus-CRT arm vs. 21% in the CRT-alone arm, and 34.7% in the nimotuzumab-plus-RT arm vs. 13% in the RT-alone arm, Dr. Lokesh Viswanath reported at the annual meeting of the American Society for Radiation Oncology.

These data were a follow-up to the 30-month survival data (presented earlier this year in a poster at the annual meeting of the American Society of Clinical Oncology) that showed overall survival rates of 69.5% when nimotuzumab was added to CRT vs. 39% with CRT alone, and 21.74% whether or not nimotuzumab was added to RT alone.

What ultimately may set nimotuzumab apart from other EGFR inhibitors is its safety profile, particularly a lower rate of severe skin toxicities. Grade 3 radiation-induced skin reactions were not observed in patients taking nimotuzumab with RT or CRT. They were present in 6.6% of RT-only patients and 5% of CRT-only patients, said Dr. Viswanath of the Kidwai Memorial Institute of Oncology, Bangalore, India. Grade 1/2 skin reactions were reported in at least two-thirds of all patients, occurring in a high of 87% of patients who were treated with CRT alone or with nimotuzumab.

Grade 3 mucositis occurred in 59.2% of the RT-alone arm, 55.5% of the RT-plus-nimotuzumab arm, 29.4% of the CRT-alone arm, and 55% of the CRT-plus-nimotuzumab arm, said Dr. Viswanath, who disclosed no conflicts of interest.

All patients received 6,600 cGy of radiation over 6-6.5 weeks. Chemoradiation consisted of weekly cisplatin given 6 hours before RT as a radio sensitizer. Nimotuzumab (200 mg) was given weekly for 6 weeks as a 60-minute infusion 3 days before RT. This schedule was chosen to differentiate its adverse events from those of cisplatin, he said.

Study discussant Dr. Kie K. Ang of the University of Texas M.D. Anderson Cancer Center in Houston questioned whether the data represent a positive signal. He noted that the small sample size of 76 evaluable patients could influence outcomes, and that patients treated with nimotuzumab were more likely to have primary tumors of the oropharynx. Such tumors, if positive for the human papillomavirus, are more responsive to chemotherapy and radiotherapy.

The study was sponsored by Biocon BioPharmaceuticals Ltd., the licensee for nimotuzumab in India.