Source: www.reuters.com
Author: press release

YM BioSciences Inc., a life sciences product development company that identifies and advances a diverse portfolio of promising cancer-related products at various stages of development, announced that an oral presentation at the American Society for Therapeutic Radiology and Oncology (ASTRO) 2009 Annual Meeting reported positive 48-month survival data for its EGFR-targeting antibody, nimotuzumab. The “BEST” trial was a randomized four-arm study treating patients with inoperable, locoregionally-advanced, stage III/IVa head and neck cancer with radiation alone, chemoradiation alone, or radiation or chemoradiation in combination with nimotuzumab.

These data were a follow-up to 30-month survival data presented at ASCO 2009 and demonstrate that the benefit of adding nimotuzumab to radiation and chemoradiation is durable and persists for several years. “These data are convincing evidence that nimotuzumab is an efficacious and safe drug and highlight its potential in the head and neck cancer indication. In this respect we note that the National Cancer Centre of Singapore has initiated a global Phase III trial with nimotuzumab in the adjuvant setting for head and neck cancer patients,” said David Allan, Chairman and CEO of YM BioSciences. “Activity of nimotuzumab in the BEST trial was similar to that demonstrated in separate trials with cetuximab in locally advanced head and neck cancer but there was no evidence that nimotuzumab’s activity was accompanied by the advanced toxicities of the class.”

In the ASTRO presentation, Dr. Lokesh Viswanth, Kidwani Memorial Institute of Oncology, Bangalore, India described that the addition of nimotuzumab to radiotherapy (RT) and chemoradiotherapy (CRT) had an important effect on overall survival. At 48 months, 41% of the patients in the nimotuzumab+CRT arm were alive compared to 21% in CRT-alone arm, and 34.7% in the nimotuzumab+RT arm were alive compared to 13% in the RT-alone arm. The difference at 48 months between CRT and nimotuzumab+CRT arms reached statistical significance (p=0.0149). Kaplan-Meier curves for survival maintained a consistent separation at the 48-month update, demonstrating that the benefit of adding a fixed course of nimotuzumab to RT and CRT persists for an extended period. Because efficacy results in the control groups in this trial were similar to those published in contemporaneous international trials in this indication, and because imbalances between the study arms were minor, authors concluded that the benefit presented in this proof of principle trial must be attributable to the activity of nimotuzumab.

The trial contained no reports of late toxicity with nimotuzumab and its benign side-effect profile continued to be demonstrated. The combination of nimotuzumab with radiotherapy and chemoradiotherapy was safe and nimotuzumab did not potentiate radiation dermatitis. As a consequence, continuing reports concerning cetuximab and its significant potentiation of severe radiation dermatitis in the treatment of head and neck cancer with radiation continues to differentiate nimotuzumab which, as first described in a poster at AACR 2009, binds selectivity to cancer tissues thereby avoiding exacerbation of damage to healthy tissues by radiation.

“This trial adds to the body of clinical data concerning the activity of nimotuzumab in head and neck cancer, which includes a number of earlier trials. The presentation at ASTRO 2009 adds an important level of understanding for nimotuzumab’s development highlighting its prospect to be the best anti-EGFR monoclonal antibody in this patient population,” said Leonardo Viana Nicacio, M.D., Director of Clinical Affairs for YM BioSciences. “The data are now shown to be reproducible in three separate studies, all of which reported nimotuzumab’s characteristically benign toxicity profile. While the chemoradiotherapy and radiotherapy protocols in BEST differ from those commonly used in North America and Europe, treatments were consistent between the arms allowing for an appropriate assessment of nimotuzumab’s activity and efficacy. These data, which suggest activity and durability similar to other anti-EGFR antibodies in this population, support the intended initiation of Phase III trials in this patient population.”

A total of 92 patients were enrolled in the BEST trial, of which 76 were considered evaluable. The trial was sponsored by Biocon Ltd., the licensee from CIMAB S.A. for nimotuzumab in India. A poster describing 30-month data from this trial was presented at the 2009 ASCO Annual Meeting and is entitled: “A Phase IIb 4-arm open-label randomized study to assess the safety and efficacy of h-R3 monoclonal antibody against EGFR in combination with chemoradiation therapy or radiation therapy in patients with advanced (Stage III or IVa) inoperable head and neck cancer”, by Reddy BK et al. (Citation: J Clin Oncol 27:15s, 2009; Abstract No: 6041; Session: Head and Neck Cancer).

The data presented at ASCO demonstrated that the addition of nimotuzumab to both the radiation and chemoradiation regimens improved the overall response rate, survival rate at 30 months, median progression-free survival and median overall survival. An unplanned, retrospective, combined group analysis of the nimotuzumab arms vs. the non-nimotuzumab arms demonstrated a significant difference in overall survival (p=0.0018) favoring nimotuzumab. The addition of nimotuzumab did not add to the severe toxicities of either regimen, with no Grade 3-4 skin toxicities observed. The authors concluded that the efficacy of nimotuzumab compares favorably to results reported for cetuximab and that this efficacy was not accompanied by the latter’s severe toxicities. They also concluded that this trial is the first randomized study in head and neck cancer to their knowledge that challenges the adopted tenet that the efficacy of EGFR inhibitors is linked to the toxicity of the class.