Tumor genomic profiling guides patients with metastatic gastric cancer to targeted treatment: The viktory umbrella trial

Jeeyun Lee, Seung Tae Kim, Kyung Kim, Hyuk Lee, Iwanka Kozarewa, Peter G.S. Mortimer, Justin I. Odegaard, Elizabeth A. Harrington, Juyoung 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 AnMin 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 Talasaz, Simon J. Hollingsworth, Kyoung Mee Kim, Won Ki Kang

Research output: Contribution to journalArticlepeer-review

150 Scopus citations

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 RIC-TOR 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), ada-vosertib (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 feasibility of tumor profiling and its clinical utility.

Original languageEnglish
Pages (from-to)1388-1405
Number of pages18
JournalCancer Discovery
Volume9
Issue number10
DOIs
StatePublished - Oct 2019

Bibliographical note

Funding Information:
This work was supported by funding from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI14C3418). Support was also provided by a grant from the 20 by 20 Project of Samsung Medical Center (GF01140111). This investigator-initiated trial was also funded by a study-drug donation and partial fund from AstraZeneca.

Funding Information:
We would like to thank Drs. Adam J. Bass, Joseph Chao, and Samuel J. Klempner for scientific discussion and critical review of our manuscript. On behalf of the VIKTORY team, we would like thank our patients and their families for their participation. This work was supported by funding from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI14C3418). Support was also provided by a grant from the 20 by 20 Project of Samsung Medical Center (GF01140111). This investigator-initiated trial was also funded by a study-drug donation and partial fund from AstraZeneca.

Publisher Copyright:
© 2019 American Association for Cancer Research.

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