Author: Michael Smith, North American Correspondent, MedPage Today
A novel antibody improved outcomes for patients with advanced and inoperable squamous cell carcinoma of the head and neck, researchers reported.
Combined with radiation or chemoradiation, the substance — a fully humanized monoclonal antibody dubbed nimotuzumab — significantly outperformed either modality alone in an open-label randomized trial, according to K. Govind Babu, MD, of Kidwai Memorial Institute of Oncology in Bangalore, India, and colleagues.
At the same time, there was little serious toxicity — such as debilitating skin rash — attributed to the compound, the researchers reported in a poster discussion session at the annual meeting of the American Society of Clinical Oncology here.
It’s the first randomized study of the drug to show clinical benefit without the toxicities associated with similar antibodies, the researchers said.
In general, neither radiation nor chemotherapy provides a good outcome for patients with inoperable stage III or IVa squamous cell carcinoma of the head and neck. However, substances such as cetuximab (Erbitux) that target the epidermal growth factor receptor (EGFR) — overexpressed in such tumors — have improved outcomes.
Nimotuzumab, like cetuximab, targets EGFR, but is highly selective for tumor tissues, limiting toxicity, the researchers said.
The study enrolled 92 patients, and 76 were evaluable for efficacy. They were treated with radiation or chemoradiation (with cisplatin), with or without nimotuzumab. The substance was given by intravenous infusion of 200 milligrams over a 60-minute period, once a week for six weeks.
In group A — radiation with or without the antibody — the locoregional response rate was 37% with radiation alone, but was 76% when nimotuzumab was added, the researchers reported. In the other group, chemoradiation and nimotuzumab led to a 100% locoregional response, compared with 70% for chemo alone, they said.
At four years of follow-up, they reported:
- The overall survival rate was 47% for patients getting the antibody and chemoradiation, compared with 21% for chemoradiation alone, a difference that was significant at P=0.01.
- The comparable rates in the radiation group were 34% for the combination and 13% for radiation alone, which were not significantly different.
- Median overall survival was not reached for chemoradiation and nimotuzumab, but was 21.9 months for chemoradiation alone. The comparable figures for radiation were 14.3 months versus 12.7 months.
- Adding nimotuzumab to chemoradiation resulted in a 65% reduction in risk of death; the hazard ratio was 0.35, which was significant at P=0.01.
The study was small, but it provides a “signal of benefit” that needs to be confirmed in larger randomized trials, according to Ranee Mehra, MD, of Fox Chase Cancer Center in Philadelphia, who was not involved in the research but who discussed it in an oral session.
She noted that the arms of the trial were imbalanced in terms of the cancer site, with a higher percentage of cancer of the oropharynx in the nimotuzumab arms.
Mehra said the results in the radiation arm don’t parallel historical data with cetuximab. In trials with that substance, the median overall survival with radiation was 29 months, and when cetuximab was added it reached 49 months.
The differences have several possible explanations, she said, including varying patient characteristics, a lower radiation dose in the nimotuzumab trial, and the effect of human papillomavirus infection, which was not recorded in this study but which plays a role in outcomes.
1. Journal of Clinical Oncology
2. Babu KG et al. “An open-label, randomized, study of h-R3mAb (nimotuzumab) in patients with advanced (stage III or IVa) squamous cell carcinoma of head and neck (SCCHN): Four-year survival results from a phase IIb study.” J Clin Oncol 28:7s, 2010 (suppl; abstr 5530)