Tumor Genomic Profiling Guides Patients with Metastatic Gastric Cancer to Targeted Treatment: The VIKTORY Umbrella Trial

作者：Jeeyun Lee, Seung Tae Kim, Kyung Kim, Hyuk Lee, Iwanka Kozarewa, Peter G. S. Mortimer, Justin Iver Odegaard, Elizabeth A. Harrington, Ju-Young Lee, Taehyang Lee, Sung Yong Oh, Jung-Hun Kang, Jung Hoon Kim, Youjin Kim, Jun Ho Ji, Young Saing Kim, Kyoung Eun Lee, Jinchul Kim, Tae Sung Sohn, Ji Yeong An, Min Gew Choi, Jun Ho Lee, Jae Moon Bae, Sung Kim, Jae J. Kim, Yang Won Min, Byung‐Hoon Min, Nayoung K. D. Kim, Sally Luke, Young Hwa Kim, Jung Yong Hong, Se Hoon Park, Joon Oh Park, Young Suk Park, Ho Yeong Lim, AmirAli H. Talasaz, Simon J. Hollingsworth, Kyoung‐Mee Kim, Won Ki Kang · 发表于：Cancer Discovery · 年份：2019 · DOI：10.1158/2159-8290.cd-19-0442 · 被引用次数：240 · 研究领域：Gastric Cancer Management and Outcomes、Colorectal Cancer Treatments and Studies、Lung Cancer Treatments and Mutations

Abstract The VIKTORY (targeted agent eValuation In gastric cancer basket KORea) trial was designed to classify patients with metastatic gastric cancer based on clinical sequencing and focused on eight different biomarker groups (RAS aberration, TP53 mutation, PIK3CA mutation/amplification, MET amplification, MET overexpression, all negative, TSC2 deficient, or RICTOR amplification) to assign patients to one of the 10 associated clinical trials in second-line (2L) treatment. Capivasertib (AKT inhibitor), savolitinib (MET inhibitor), selumetinib (MEK inhibitor), adavosertib (WEE1 inhibitor), and vistusertib (TORC inhibitor) were tested with or without chemotherapy. Seven hundred seventy-two patients with gastric cancer were enrolled, and sequencing was successfully achieved in 715 patients (92.6%). When molecular screening was linked to seamless immediate access to parallel matched trials, 14.7% of patients received biomarker-assigned drug treatment. The biomarker-assigned treatment cohort had encouraging response rates and survival when compared with conventional 2L chemotherapy. Circulating tumor (ctDNA) analysis demonstrated good correlation between high MET copy number by ctDNA and response to savolitinib. Significance: Prospective clinical sequencing revealed that baseline heterogeneity between tumor samples from different patients affected response to biomarker-selected therapies. VIKTORY is the first and largest platform study in gastric cancer and supports both the feas...