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1、2016 ASCO 晚期胃癌的治疗进展 张小田 北京大学肿瘤医院 消化内科 2016 ASCO 晚期胃癌进展概要 化疗方案 全身化疗： Abs 4015-III期 SOPP 研究：晚期一线 方案 SOX vs. SP Abs 4016-III期 DREAM 研究: 口服紫杉醇 vs . 静脉紫杉醇 腹腔化疗： Abs 4014-III期 PHOENIX研究： 腹腔+静脉紫杉醇+S1 vs. SP 靶向治疗药物 抗CLDN18.2抗体：IMAB362 LBA4001-II期 FAST 研究：EOX + IMAB362 vs. EOX 免疫治疗药物 抗PD-(L)1 Abs 4009-Ib期 JA
2、VELIN solid tumor 研究：Avelumab单药 Abs 4037-II期 KEYNOTE-059 研究：Pembro vs. Pembro +CDDP+5-Fu/Cape 抗PD-L1+抗CTLA4 Abs 4010-I/II期 CheckMate-032研究: Nivo (anti-PD-L1) vs nivo+ipi(anti CTLA-4) 抗CTLA-4 Abs 4011-II期研究 一线化疗后，ipi (anti-CTL-4)+ BSC vs. BSC SOX vs SP：晚期胃癌一线治疗的III期研究 SOPP 研究（韩国） n= 338 研究设计 R SOX S-
3、1：1-14天 奥沙利铂：每3周 1次 SP S-1：1-14天 顺铂：每3周1 次 S-1: 40mg/m2, Bid 奥沙利铂: 130mg/m2，iv S-1: 40mg/m2, Bid 顺铂：60mg/m2，iv 研究类型： III期RCT，非劣效性研究 研究目的 ： 晚期胃癌一线治疗 SOX 丌亚亍 SP 研究对象： 初治晚期胃癌患者，ECOG 0-2 研究终点： 主要终点：PFS 次要终点：OS、ORR、安全性 一项开放性标签、随机、多中心、非劣效性III期研究 SOX值(%) SP值（%） P FAS中患者数 173 164 男性 123（71） 106（65） 0.204 中位
4、年龄 58（29-80） 55（26-78） 0.051 中位BMI 21.9（14.1-31.6）21.6(14.3-34.9) 0.267 入组时状态 初始转移性 复发性 可切除转移性 128（74） 27（16） 18（10） 127(77) 27(17) 10(6) 0.359 可测量病灶 92（53） 81(49) 0.552 ECOG体能 0-1 2 170（98） 3（2） 160(98) 4(2) 0.372 基线特征 无进展生 存 生存概率 自随机起时间（月） 共计 事件数 中位PFS 总生存 生存概率 自随机起时间（月） 共计 事件数 中位PFS 结果: PFS 82:35
5、9-74.Rationale for sample size calculation Estimated MST: IP 22 months, SP 11 months Accrual period 2 years, follow-up period 2 years Two-sided =0.05, =0.1, sample size ratio IP:SP = 2:1 180 patients (IP 120, SP 60)Phase III study of intraperitoneal paclitaxel plus S-1/paclitaxel compared with S-1/c
6、isplatin in gastric cancer patients with peritoneal metastasis: Hironori Ishigami1, Yoshiyuki Fujiwara2, Ryoji Fukushima3, Atsushi Nashimoto4, Hiroshi Yabusaki5, Haruhiko Imamoto6, Motohiro Imano6, Yasuhiro Kodera7, Yoshikazu Uenosono8, Kenji Amagai9, Shigenori Kadowaki10, Hiroto Miwa11, Takuhiro Ya
7、maguchi12, Hironori Yamaguchi13, Toshiaki Watanabe1, Joji Kitayama13, Japan intraperitoneal chemotherapy study group (JIPG)1 The University of Tokyo, 2 Osaka Medical Center for Cancer and Cardiovascular Disease, 3 Teikyo University, 4 Nanbugo General Hospital, 5 Niigata Cancer Center Hospital, 6 Kin
8、ki University, 7 Nagoya University, 8 Kagoshima University, 9 Ibaraki Prefectural Central Hospital, 10 Aichi Cancer Center Hospital, 11 Hyogo College of Medicine, 12 Tohoku University, 13 Jichi Medical University, JapanIP PTX plus S-1/PTX Phase I studyPTX was diluted in 1 liter of normal saline, and
9、 administered through a port or catheter over 1 hour concurrently with IV PTX. Maximum-tolerated dose (MTD) 30 mg/m2(level 2) Recommended dose (RD)20 mg/m2(level 1) Dose-limiting toxicities (DLT)neutropenia, diarrheaIshigami H et al. Oncology 2009; 76: 311-314. Phase II study (follow-up data) Advers
10、e events (Grade 3/4): leukopenia (18%), neutropenia (38%), anemia (10%), anorexia (5%), nausea (8%) Ishigami H et al. Ann Oncol 2010; 21: 6770. Response to IP chemotherapyBackground: Intraperitoneal (IP) paclitaxel (PTX) provides sustained high local concentrations, and its efficacy has been shown i
11、n ovarian cancer. We developed a regimen combining IP PTX with S-1/PTX for the treatment of gastric cancer patients, and obtained promising results with a one-year overall survival (OS) rate of 78% in a phase II study. This multicenter phase III study evaluated the efficacy of IP PTX plus S-1/PTX co
12、mpared to standard systemic chemotherapy. Methods: Eligibility criteria included pathologically confirmed gastric adenocarcinoma, peritoneal metastasis, and no or short-term (2 months) prior chemotherapy. Patients were randomized 2:1 to an IP (IP PTX plus S-1/PTX; IP PTX 20 mg/m2, intravenous IV PTX
13、 50 mg/m2on days 1 and 8, and S-1 80 mg/m2/day on days 1-14, q3 weeks) arm or a SP (S-1/cisplatin; IV cisplatin 60 mg/m2on day 8, and S-1 80 mg/m2/day on days 1-21, q5 weeks) arm. Randomization was stratified by center, having received prior chemotherapy, and the extent of peritoneal disease. The pr
14、imary endpoint was OS. Secondary endpoints were response rate and safety. Results: Between October 2011 and November 2013, 183 patients were enrolled, and 164 patients were included in the efficacy analysis. Baseline patient characteristics were balanced between the two arms except for ascites. Of 4
15、5 patients with massive ascites (beyond the pelvic cavity), 38 (84%) were randomized to the IP arm and 7 (16%) to the SP arm. The median OS for IP and SP were 17.7 and 15.2 months, respectively (stratified log-rank test, p=0.080; hazard ratio HR 0.72, 95% confidence interval CI 0.49-1.04, p=0.081).
16、For a sensitivity analysis using a stratified Cox regression model, adjusting for the baseline ascites, the HR was 0.59 (95%CI 0.39-0.87, p=0.0079). The overall response rate was 53% in the IP arm, and 60% in the SP arm (p=1.0). Both regimens were tolerable, and there were no treatment-related deaths. Conclusions: The primary analysis did
