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2015年ASCO GI研讨会于1月15日～17日在美国旧金山举行。目前，S-1+顺铂（SP）是东亚地区晚期胃癌（AGC）的标准治疗方案。在HER2-阳性ACG患者中，ToGA试验显示通过增加曲妥珠单抗到卡培他滨联合顺铂或者氟尿嘧啶联合顺铂方案中会带来生存获益，HERBIS-1试验证明将曲妥珠单抗增加到SP方案是有希望的抗肿瘤活性。
然而，顺铂有几个重要的缺点，包括恶性，呕吐，和肾毒性。顺铂的这些缺点在老年患者中尤为明显。在1月15日食管癌和胃癌壁报区展出了一项研究对曲妥珠单抗单独联合S-1在老年HER-2阳性AGC患者中的疗效和安全性进行了评估。
研究方法
将≥65岁的HER-2阳性ACG患者，在第1～28天（42天为一个周期）接受S-1（80～120mg/d）口服，第1天（21天为一个周期）静脉注射曲妥珠单抗（第一次，8mg/kg；第二次，6mg/kg）。主要终点是缓解率（RR）；次要终点是总生存期（OS），无进展生存期（PFS），治疗失败时间（TTF）和不良事件。样本量是40～60名患者，预估的阈值基线RR=20%，预期的RR=35%，α=0.1（单侧），以及P=80～90%。
研究结果
一共有51例患者入组。一例患者不符合条件，因此在50例患者的全面分析集中（实际统计P=87.5%），中位年龄数是71岁（范围65～85），男女比例为37:13，ECOG PS是0/1/2=33/14/3。已证实RR（CR/PR/SD/PD=3/17/23/7）是40.0%（80%置信区间[CI]；31.1～48.9%，95% CI；26.4～53.6%），零假设被拒绝。疾病控制率是86%（95% CI；76.4~95.6%）。中位OS，PFS，和TTF尚不成熟。
主要的3或4级不良事件包括中性粒细胞减少（10.0%），贫血（24.0%），腹泻（10.0%）和食欲减退（12.0%）。出现1例与治疗相关的死亡。
研究结论
主要终点符合要求。曲妥珠单抗只联合S-1在老年HER2-阳性AGC患者中显示在抗肿瘤活性上有希望，而且是可控制的毒性作用。临床试验信息：UMIN000007368。
英文摘要：
Multicenter phase II study of trastuzumab with S-1 alone in elderly patients with HER-2 positive advanced gastric cancer（JACCRO GC-06）.（Abstract 106）
Background：S-1 plus cisplatin (SP) is a standard regimen for advanced gastric cancer (AGC) in East Asia. In patients with HER2-positive AGC, ToGA trial showed survival benefit with the addition of trastuzumab to capecitabine plus cisplatin or fluorouracil plus cisplatin and HERBIS-1 trial demonstrated promising antitumor activity with the addition of trastuzumab to SP. However, cisplatin has several important drawbacks, including nausea, vomiting, and renal toxicity. And these disadvantages of cisplatin are noticeable in elderly patients. We evaluated the efficacy and safety of trastuzumab combined with S-1 alone in elderly patients with HER-2 positive AGC.
Methods：Patients, 65 years or older, with HER2-positive AGC received S-1 (80–120mg per day) orally on days 1–28 of a 42-day cycle and trastuzumab (course 1, 8 mg/kg; course 2 onward, 6 mg /kg) intravenously on day 1 of a 21-day cycle. The primary end point was response rate (RR); secondary endpoints were overall survival (OS), progression free survival (PFS), time to treatment failure (TTF) and adverse events. The sample size was 40 to 60 patients estimated on the basis of threshold RR=20%, expected RR=35%, alpha=0.1 (one-sided) and power=80 to 90%.
Results：A total of 51 patients were enrolled. One patient was ineligible, therefore in the full analysis set of 50 patients (actual statistical power = 87.5%), the median age was 71 years (range=65-85), male: female was 37:13 and ECOG PS was 0/1/2= 33/14/3. The confirmed RR (CR/PR/SD/PD=3/17/23/7) was 40.0% (80% confidence interval (CI); 31.1-48.9%, 95% CI; 26.4-53.6%), and the null hypothesis was rejected. The disease control rate was 86.0% (95% CI; 76.4-95.6%). Median OS, PFS, and TTF were immature. Major grade 3 or 4 adverse events included neutropenia (10.0%), anemia (24.0%), diarrhea (10.0%) and anorexia (12.0%). There was one treatment-related death.
Conclusions：The primary end point was met. Trastuzumab in combination with S-1 alone demonstrated promising antitumor activity and manageable toxic effects in elderly patients with HER2-positive AGC. Clinical trial information: UMIN000007368.
查看会议专题》》》2015 ASCO胃肠肿瘤(GI)研讨会
