ORLANDO (EGMN) – The addition of trastuzumab to standard chemotherapy for patients with HER2-positive advanced gastric cancer improves outcomes without sacrificing quality of life for patients, based on an analysis of data from a pivotal phase III study of nearly 600 patients.
Global health status, physical function, symptoms, pain, and use of pain medications were comparable whether or not patients received trastuzumab with a regimen of capecitabine or fluorouracil plus cisplatin, Dr. Taroh Satoh reported at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
“Trastuzumab plus chemotherapy improves overall survival and progression-free survival versus chemotherapy alone, without compromising quality of life,” said Dr. Satoh of Kinki University in Osaka, Japan.
The findings are important given that patients will usually spend more than half of their remaining life on treatment, according to Dr. David Cunningham, who presented a discussion of the report. “Small gains in survival should not be at the expense of quality of life,” he said.
The Trastuzumab for Gastric Cancer (ToGA) trial randomized 290 HER2-positive patients to capecitabine or 5-fluorouracil (5-FU) and cisplatin and 294 to capecitabine or 5-fluorouracil (5-FU) and cisplatin plus trastuzumab. The primary end point of the study, overall survival, was significantly longer in the trastuzumab arm (13.8 months) compared with chemotherapy alone (11.1 months), as reported at the 2009 ASCO annual meeting. It was the first trial to show a benefit from targeting HER2 in HER2-positive gastric cancer with trastuzumab, up to now a drug used exclusively in HER2-positive breast cancer.
Capecitabine was delivered at 1,000 mg/m2 twice daily on days 1-14 every 3 weeks for six cycles. 5-FU was given in continuous IV infusion at 800 mg/m2 on days 1-5 every 3 weeks for six cycles. Cisplatin was delivered at 80 mg/m2 every 3 weeks for six cycles. Trastuzumab was given in an 8-mg/kg loading dose followed by 6 mg/kg every 3 weeks until disease progression.
Quality of life was evaluated for the full analysis set population at day 1 and every 3 weeks (prior to drug administration) until disease progression. Investigators used two measures: the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 (version 3.0) and the EORTC QLQ-STO22 questionnaires. The EORTC QLG-C30 assesses global health status, including functional and symptom scales. The EORTC QLQ-STO22 was a disease-specific module for gastric cancer. Symptom scales for the tool include disease, treatment-related symptoms, side effects, dysphagia, nutrition, and emotional problems. Scores for each tool range from 0-100.
In addition, pain intensity was assessed using a visual analog scale (VAS). Analgesic consumption for gastric pain was also assessed.
At baseline, more than 95% of patients in both treatment arms completed both questionnaires. Throughout the study, the completion rate was slightly greater for the trastuzumab arm. “We strongly believe that this is because of the extension of progression-free survival with trastuzumab,” said Dr. Satoh.
The mean EORTC QLQ-C30 global health status score improved over time for both arms, with no significant difference between the arms. “Trastuzumab was comparable to, if not better than, the chemotherapy-alone arm,” he said.
These findings should be interpreted in light of diminishing patient completion of the quality of life questionnaires, said Dr. Cunningham. While global health status scores for both groups improved following discontinuation of chemotherapy, the number of patients who completed quality of life questionnaires at that time was relatively small – 36 (13%) in the chemotherapy-alone arm and 87 (30%) patients in the trastuzumab arm at week 34.
“This is a self-selected population,” said Dr. Cunningham, head of the gastrointestinal and lymphoma units at the Royal Marsden Hospital in London
On the physical functioning component, scores in both arms only began to improve after treatment was completed. Similar trends were seen for emotional and social function, said Dr. Satoh. Nausea and vomiting symptom scores improved over time for both arms. Similar trends were seen for appetite and constipation.
Looking at the EORTC QLQ-STO22 results, dysphagia scores in both arms started to improve during treatment, and continued to improve after treatment was stopped; no significant difference was seen between the arms. Similar trends were seen for body image and hair loss scores.
There was no significant difference between the arms over time in VAS pain intensity scores. At baseline, 29% of patients used analgesic medications. During the course of the study, 2% in the trastuzumab arm and 6% in the chemotherapy-alone arm discontinued at least one medication. While 7% on trastuzumab and 6% given chemotherapy alone had no change in their medications, 20% and 17%, respectively, increased the dose or added at least one medication.
“Considering the prolongation of progression-free survival in the trastuzumab arm, this is quite important data,” said Dr. Satoh. “We don’t have to compromise pain of patients when we deliver trastuzumab.”
The study was sponsored by Hoffmann-La Roche. Trastuzumab (Herceptin) is marketed in the United States by Genentech, in Japan by Chugai, and in Europe by Roche. Dr. Satoh reported that he received travel support from Roche. He also has received consultancy fees from several pharmaceutical companies. Several co-authors are employed by Roche.
Dr. Cunningham reported that he is a consultant for and has received research funding from several pharmaceutical companies, including Roche.
Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.
奥兰多(EGMN)——根据对一项纳入近600例患者的III期关键研究数据的分析，对于HER2-阳性的晚期肺癌患者，在标准化疗方案中追加曲妥珠单抗不仅可改善预后，并且不会导致患者生活质量降低。
接受卡培他滨或氟尿嘧啶加顺铂化疗方案并追加或不追加曲妥珠单抗治疗的患者整体健康状况、身体功能、症状、疼痛以及镇痛药物的使用情况均相似，Taroh Satoh医生在美国临床肿瘤学会主办的一次关于胃肠癌症的会议上报告。
“与单纯接受标准化疗方案相比，化疗加曲妥珠单抗的方案可延长总生存期和无进展生存期，且对生活质量无不利影响，”日本大阪市近畿大学的Satoh医生说。
因为这些患者剩余生命中一半以上的时间需要接受治疗，所以这一发现的意义非常重大，David Cunningham医生在对研究报告的讨论中说。“生存期的小幅度延长不应以牺牲生活质量为代价。”他说。
曲妥珠单抗治疗胃癌(ToGA)试验中，290例HER2阳性患者随机接受卡培他滨或5-氟尿嘧啶(5-FU)加顺铂治疗，另外294例患者随机接受卡培他滨或5-FU加顺铂和曲妥珠单抗治疗。研究主要终点为总生存期，根据在2009年ASCO年会上的报告， 曲妥珠单抗组患者生存期(13.8个月)较单纯化疗组(11.1 个月)显著延长。这是首项显示对HER2-阳性胃癌患者采用HER2为靶向的曲妥珠单抗治疗可获益的试验，到目前为止，这种药物还仅仅是用于HER2-阳性乳腺癌的治疗。
两种方案的每个治疗周期均为3周，卡培他滨的用法为在每个周期第1~14天给予1,000 mg/m2 ，每日两次，连续使用6个周期。5-FU的用法为在每个周期的第1~5天连续静脉输注，剂量为800 mg/m2 ，连续使用6个周期。顺铂的用法为每个周期给予80 mg/m2 ，连续使用6个周期。曲妥珠单抗的用法为先给予1个8mg/kg 的负荷量，以后每3周再给予6 mg/kg治疗，连续使用，直至疾病进展。
在研究第1天对全部分析集人群评估生活质量，以后每3周重复1次(用药前)，直至疾病进展。研究者使用两个生活质量评估标准：欧洲癌症研究与治疗组织(EORTC) QLQ-C30 (3.0版本)和EORTC QLQ-STO22问卷。EORTC QLG-C30评估的是整体健康状况，包括功能和症状评分。EORTC QLQ-STO22是一个胃癌疾病特异性模块。该工具中的症状评分包括疾病、治疗相关症状、副反应、吞咽困难、营养和情感问题。每一工具的评分范围为0~100分。
另外，使用视觉模拟量表(VAS)评估疼痛强度。并对胃癌疼痛所致镇痛药物消耗量进行评估。
基线时，两治疗组均有95%以上的患者完成了上述两种问卷。研究期间，曲妥珠单抗治疗组患者的问卷完成率略高。“我们的观点强烈支持这是曲妥珠单抗治疗组患者无进展生存期延长的结果。” Satoh医生说。
两治疗组的平均EORTC QLQ-C30整体健康状况评分均随时间改善，无统计学差异。“即使曲妥珠单抗治疗组不优于单纯化疗组，也至少与单纯化疗组效果相当。”他说。
Cunningham医生说，对这些结果的解释中应考虑到完成生活质量问卷的患者在逐渐减少的影响。尽管停用化疗后两组患者的整体健康状况评分均有改善，但此时完成生活质量问卷的患者数相对较少，研究第34周时，单纯化疗组完成生活质量问卷的患者数为36例 (13%)，曲妥珠单抗治疗组为87例 (30%)。
“这是一个自我选择的群体。”英国伦敦皇家马斯登医院胃肠肿瘤与淋巴瘤科主任Cunningham医生说。
在治疗完成后，两组患者身体功能部分的评分方开始改善。情感和社会功能评分变化也呈现相似趋势，Satoh医生说。两组恶心和呕吐症状评分均随时间改善。食欲和便秘症状评分变化也呈现相似趋势。
EORTC QLQ-STO22问卷评估结果是，两组吞咽困难症状评分于治疗期间开始改善，并且在停用治疗后评分继续改善；两组无统计学差异。体像和脱发评分变化也呈现相似趋势。
两组VAS疼痛强度评分随时间的变化无统计学差异。基线时，29%的患者使用镇痛药物治疗。研究过程中，曲妥珠单抗组2%的患者和单纯化疗组6%的患者至少减少1次用药，两组中治疗无变化的患者分别占7%和 6%，另外，两组分别有20%和17%的患者增加药物剂量或至少增加1次用药。
“考虑到曲妥珠单抗治疗组无进展生存期延长的结果，使这一数据显得更为重要，” Satoh医生说。“这表明曲妥珠单抗治疗对患者的疼痛症状无不利影响。”
该研究由豪夫迈罗氏公司赞助。曲妥珠单抗(赫塞汀)在美国的销售商为基因泰克公司，在日本为中外制药公司，在欧洲为罗氏公司。Satoh医生报告接受了罗氏公司资助的差旅费，他还接受了一些医药公司提供的咨询费。另外，有一些合著者为罗氏公司雇员。
Cunningham医生报告他作为一些医药公司的顾问并接受了一些公司提供的研究资助，其中包括罗氏公司。
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