MET Inhibitor as a Monotherapy in GI Cancers: Unlikely Beneficial

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A select group of patients with MET-amplified gastric/gastroesophageal junction/esophageal (G/GEJ/E) adenocarcinoma could benefit from AMG 337.
A select group of patients with MET-amplified gastric/gastroesophageal junction/esophageal (G/GEJ/E) adenocarcinoma could benefit from AMG 337.

The small-molecule MET inhibitor AMG 337 showed antitumor activity in MET-amplified gastric/gastroesophageal junction/esophageal (G/GEJ/E) adenocarcinoma, with an overall response rate of 18%, according to a recent study.1 However, this study was terminated after a review showed the overall response rate was lower than expected based on preliminary data from another separate study of AMG 337.2

“As of July 2014, the first-in-human study had shown responses in 8 of 13 (62%) patients with MET-amplified G/GEJ/E adenocarcinoma […] suggesting that the response rate in this study, which only enrolled patients with MET-amplified tumors, would be high,” the researchers wrote.

In this phase 2 study, 2 cohorts were examined. Cohort 1 was 45 patients with MET-amplified G/GEJ/E adenocarcinoma and cohort 2 was 15 patients with MET-amplified solid tumors. The majority of patients had metastatic disease (97%) and had either 1 (29%), or 2 or more (69%), prior lines of therapy.

Overall, 58 patients received at least 1 dose of the study drug. The overall response rate in cohort 1 was 18%, including 8 partial responses. None of the patients in cohort 2 responded to the investigational agent.

Looking at outcomes in 54 evaluable patients, the median progression-free survival was 3.4 months and the median overall survival was 7.9 months.

Commonly occurring adverse events including headache, nausea, vomiting, abdominal pain, decreased appetite, and peripheral edema. The majority of patients (71%) had grade 3 or worse adverse events and 59% had serious adverse events.

“Although it is unlikely that monotherapy would be beneficial in a large group of patients, it is possible that a select group of patients could benefit from AMG 337 or that combination therapy strategies could be useful; however, such approaches would require further study,” the researchers wrote.

Disclosure: The original study was funded by Amgen Inc. For a full list of disclosures, please refer to the original study.

References

  1. Van Cutsem E, Karaszewska B, Kang Y, et al. A multicenter phase 2 study of AMG 337 in patients with MET-amplified gastric/gastroesophageal junction/esophageal adenocarcinoma and other solid tumors [published online October 26, 2018]. Clin Cancer Res. doi: 10.1158/1078-0432.CCR-18-1337
  2. Kwak EL, LoRusso P, Hamid O, et al. Clinical activity of AMG 337, on oral MET kinase inhibitor, in adult patients (pts) with MET-amplified gastroesophageal junction (GEJ), gastric (G), or esophageal (E) cancer [abstract]. J Clin Oncol. 2015;33(3_suppl);1-1. doi: 10.1200/jco.2015.33.3_suppl.1

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