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.
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芝加哥(EGMN)——据来自BEST临床试验的长期观察结果，尼妥珠单抗(nimotuzumab)与放射治疗(RT)和放化疗(CRT)联合可延长晚期头颈部恶性肿瘤患者的生存时间，且无严重的药物相关毒性。
尼妥珠单抗是针对表皮生长因子受体(EGFR)的单克隆抗体，在美国和加拿大，其正处于针对众多恶性肿瘤的后期开发阶段。
这项4组Ⅱb期开放性研究将92例无法手术的Ⅲ/Ⅳa期头颈部恶性肿瘤患者随机分入单纯RT治疗组、单纯CRT治疗组、RT联合尼妥珠单抗治疗组和CRT联合尼妥珠单抗治疗组。
Lokesh Viswanath博士在美国放射肿瘤学会年会上报告称，48个月后，CRT联合尼妥珠单抗治疗组患者总体生存率为52%，而单纯CRT治疗组为21%；RT联合尼妥珠单抗治疗组为34.7%，而单纯RT治疗组为13%。
以上数据为30个月生存数据(在今年早些时候美国临床肿瘤学会年会壁报上所展示的)随访结果，当时报告的数据为尼妥珠单抗联合CRT治疗组总体生存率为69.5%，单纯CRT治疗组为39%；而那些接受RT治疗(无论是否联合尼妥珠单抗)的患者总体生存率为21.74%。
最终可把尼妥珠单抗与其他EGFR抑制剂区分开来的是其安全性，特别是极少发生严重皮肤毒性。印度班加罗尔Kidwai纪念肿瘤研究所的Viswanath博士说，联合应用尼妥珠单抗和RT或CRT治疗的患者中未发现辐射诱发的3级皮肤反应，而其在单纯应用RT或CRT治疗组的发生率分别为6.6%和5%。至少2/3的患者报告发生了1/2级皮肤反应，单纯应用CRT或联合尼妥珠单抗治疗者的发生率最高，为87%。
Viswanath博士说，单纯接受RT治疗组3级黏膜炎的发生率为59.2%，RT联合尼妥珠单抗治疗组为55.5%，单纯CRT治疗组为29.4%，CRT联合尼妥珠单抗治疗组为55%。Viswanath博士声明无利益冲突。
所有患者均接受为期6.0~6.5周的6,600 cGy剂量的照射。放化疗方案包括在每周RT治疗6小时前给予顺铂(作为放射增敏剂)。每周给予200 mg尼妥珠单抗，共6周，接受RT治疗前3天在60 min内注射完。他说，这一方案之所以被选用，是要将其不良反应与顺铂区分开来。
该研究的评论者，即来自美国休斯顿德克萨斯大学M.D.Anderson肿瘤中心的Kie K. Ang博士质疑这一结果是否是积极信号。他提出，研究中可评价的76例患者的样本量较小，可能影响结果，另外接受尼妥珠单抗治疗者更多为原发性口咽肿瘤患者。而人乳头瘤病毒阳性的肿瘤则对化疗和放疗更为敏感。
此项研究由印度尼妥珠单抗专利拥有者Biocon生物制药公司资助。
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