[2015 ASCO GI]曲妥珠單抗+S-1對HER-2陽性晚期胃癌療效如何？
2015-01-19 來源：醫脈通
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2015年ASCO GI研討會於1月15日～17日在美國舊金山舉行。目前，S-1+順鉑（SP）是東亞地區晚期胃癌（AGC）的標準治療方案。在HER2-陽性ACG患者中，ToGA試驗顯示通過增加曲妥珠單抗到卡培他濱聯合順鉑或者氟尿嘧啶聯合順鉑方案中會帶來生存獲益，HERBIS-1試驗證明將曲妥珠單抗增加到SP方案是有希望的抗腫瘤活性。
然而，順鉑有幾個重要的缺點，包括惡性，嘔吐，和腎毒性。順鉑的這些缺點在老年患者中尤為明顯。在1月15日食管癌和胃癌壁報區展出了一項研究對曲妥珠單抗單獨聯合S-1在老年HER-2陽性AGC患者中的療效和安全性進行了評估。
研究方法
將≥65歲的HER-2陽性ACG患者，在第1～28天（42天為一個周期）接受S-1（80～120mg/d）口服，第1天（21天為一個周期）靜脈注射曲妥珠單抗（第一次，8mg/kg；第二次，6mg/kg）。主要終點是緩解率（RR）；次要終點是總生存期（OS），無進展生存期（PFS），治療失敗時間（TTF）和不良事件。樣本量是40～60名患者，預估的閾值基線RR=20%，預期的RR=35%，α=0.1（單側），以及P=80～90%。
研究結果
一共有51例患者入組。一例患者不符合條件，因此在50例患者的全面分析集中（實際統計P=87.5%），中位年齡數是71歲（範圍65～85），男女比例為37:13，ECOG PS是0/1/2=33/14/3。已證實RR（CR/PR/SD/PD=3/17/23/7）是40.0%（80%置信區間[CI]；31.1～48.9%，95% CI；26.4～53.6%），零假設被拒絕。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級不良事件包括中性粒細胞減少（10.0%），貧血（24.0%），腹瀉（10.0%）和食慾減退（12.0%）。出現1例與治療相關的死亡。
研究結論
主要終點符合要求。曲妥珠單抗只聯合S-1在老年HER2-陽性AGC患者中顯示在抗腫瘤活性上有希望，而且是可控制的毒性作用。臨床試驗信息：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.
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