Trastuzumab Combined With Ramucirumab and Paclitaxel in Patients With Previously Treated Human Epidermal Growth Factor Receptor 2-Positive Advanced Gastric or Gastroesophageal Junction Cancer

被引：26

作者：

Kim, Chang Gon ^{[1
]}

Jung, Minkyu ^{[1
]}

Kim, Hyo Song ^{[1
]}

Lee, Choong-kun ^{[1
]}

Jeung, Hei-Cheul ^{[2
]}

Koo, Dong-Hoe ^{[3
]}

Bae, Woo Kyun ^{[4
]}

Zang, Dae Young ^{[5
]}

Kim, Bum Jun ^{[5
]}

Kim, Hyunki ^{[6
]}

Yun, Un-Jung ^{[1
,7
]}

Che, Jingmin ^{[7
,8
]}

Park, Sejung ^{[7
]}

Kim, Tae Soo ^{[7
]}

Kwon, Woo Sun ^{[7
]}

Park, Juin ^{[7
,9
]}

Cho, Sang Woo ^{[7
,10
]}

Nam, Chung Mo ^{[11
]}

Chung, Hyun Cheol ^{[1
]}

Rha, Sun Young ^{[1
,10
]}

机构：

[1] Yonsei Univ, Yonsei Canc Ctr, Dept Internal Med, Div Med Oncol,Coll Med, Seoul, South Korea

[2] Yonsei Univ, Gangnam Severance Hosp, Dept Internal Med, Div Med Oncol,Coll Med, Seoul, South Korea

[3] Sungkyunkwan Univ, Kangbuk Samsung Hosp, Dept Internal Med, Div Hematol Oncol,Sch Med, Seoul, South Korea

[4] Chonnam Natl Univ, Med Sch, Dept Internal Med, Div Hematol Oncol,Hwasun Hosp, Hwasun, South Korea

[5] Hallym Univ, Coll Med, Dept Internal Med, Div Hematol Oncol,Med Ctr, Anyang, South Korea

[6] Yonsei Univ, Dept Pathol, Coll Med, Seoul, South Korea

[7] Yonsei Univ, Songdang Inst Canc Res, Coll Med, Seoul, South Korea

[8] MD Biolab Co Ltd, Seoul, South Korea

[9] Yonsei Univ, Dept Med, Coll Med, Seoul, South Korea

[10] Yonsei Univ, Brain Korea 21 PLUS Project Med Sci, Coll Med, Seoul, South Korea

[11] Yonsei Univ, Dept Prevent Med, Coll Med, Seoul, South Korea

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2023年 / 41卷 / 27期

关键词：

PHASE-II TRIAL; BREAST-CANCER; PLUS PACLITAXEL; OPEN-LABEL; BEVACIZUMAB; COMBINATION; LAPATINIB; THERAPY; ANGIOGENESIS; CAPECITABINE;

D O I：

10.1200/JCO.22.02122

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSETrastuzumab-containing chemotherapy is the recommended first-line regimen for human epidermal growth factor receptor 2 (HER2)-positive advanced gastric or gastroesophageal junction (G/GEJ) cancer. We evaluated the safety and efficacy of trastuzumab combined with ramucirumab and paclitaxel as second-line treatment for HER2-positive G/GEJ cancer.PATIENTS AND METHODSPatients with HER2-positive advanced G/GEJ cancer who progressed after first-line treatment with trastuzumab-containing chemotherapy were enrolled from five centers in the Republic of Korea. Patients were administered a 28-day cycle of trastuzumab (once on days 1, 8, 15, and 22: 2 mg/kg followed by 4 mg/kg loading dose), ramucirumab (once on days 1 and 15: 8 mg/kg), and paclitaxel (once on days 1, 8, and 15: dose level 1, 80 mg/m2; or dose level -1, 70 mg/m2). Phase II was conducted with the recommended phase II dose (RP2D). Primary end points were determination of RP2D during phase Ib and investigator-assessed progression-free survival (PFS) in patients treated with RP2D.RESULTSDose-limiting toxicity at dose level 1 was not documented during phase Ib, and a full dose combination was selected as the RP2D. Among 50 patients with a median follow-up duration of 27.5 months (95% CI, 17.4 to 37.6), median PFS and overall survival were 7.1 months (95% CI, 4.8 to 9.4) and 13.6 months (95% CI, 9.4 to 17.7), respectively. Objective response rate was 54% (27 of 50, including one complete response), and disease control rate was 96% (48 of 50). Loss of HER2 expression was observed in 34.8% (8 of 23) patients after first-line treatment, and no definite association between HER2 expression and the outcome was revealed. Safety profiles were consistent with previous reports.CONCLUSIONTrastuzumab combined with ramucirumab and paclitaxel showed appreciable efficacy with manageable safety profiles in patients with previously treated HER2-positive G/GEJ cancer.

引用

页码：4394 / +

页数：19

共 44 条

[41] Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial [J].

Wilke, Hansjochen ;

Muro, Kei ;

Van Cutsem, Eric ;

Oh, Sang-Cheul ;

Bodoky, Gyoergy ;

Shimada, Yasuhiro ;

Hironaka, Shuichi ;

Sugimoto, Naotoshi ;

Lipatov, Oleg ;

Kim, Tae-You ;

Cunningham, David ;

Rougier, Philippe ;

Komatsu, Yoshito ;

Ajani, Jaffer ;

Emig, Michael ;

Carlesi, Roberto ;

Ferry, David ;

Chandrawansa, Kumari ;

Schwartz, Jonathan D. ;

Ohtsu, Atsushi .

LANCET ONCOLOGY, 2014, 15 (11) :1224-1235

[42]

Yagi S, 2019, GASTRIC CANCER, V22, P518, DOI 10.1007/s10120-018-0887-x

[43] A Retrospective Analysis for Patients with HER2-Positive Gastric Cancer Who Were Treated with Trastuzumab-Based Chemotherapy: In the Perspectives of Ethnicity and Histology [J].

Yi, Jun Ho ;

Kang, Jung Hun ;

Hwang, In Gyu ;

Ahn, Hee Kyung ;

Baek, Hyun Jin ;

Lee, Soon Il ;

Lim, Do Hyoung ;

Won, Young-Woong ;

Ji, Jun Ho ;

Kim, Hyo Song ;

Rha, Sun Young ;

Oh, Sung Yong ;

Lee, Kyung Eun ;

Lim, Taekyu ;

Maeng, Chi Hoon ;

Kim, Moon Jin ;

Kim, Seung Tae ;

Lee, Jeeyun ;

Park, Joon Oh ;

Park, Young Suk ;

Lim, Ho Yeong ;

Kang, Won Ki ;

Park, Se Hoon .

CANCER RESEARCH AND TREATMENT, 2016, 48 (02) :553-560

[44] Functional Genetic Approach Identifies MET, HER3, IGF1R, INSR Pathways as Determinants of Lapatinib Unresponsiveness in HER2-Positive Gastric Cancer [J].

Zhang, Zhe ;

Wang, Jiping ;

Ji, Dongmei ;

Wang, Chenchen ;

Liu, Rujiao ;

Wu, Zheng ;

Liu, Lian ;

Zhu, Dan ;

Chang, Jinjia ;

Geng, Ruixuan ;

Xiong, Lei ;

Fang, Qiangyi ;

Li, Jin .

CLINICAL CANCER RESEARCH, 2014, 20 (17) :4559-4573

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