Novel Anti-Metabolite Offers New Therapeutic Option For Resistant Colon Cancer

Howard S. Hochster, MD Associate Director, Yale Cancer Center Professor of Medicine, Yale School of Medicine New Haven, CT 06520MedicalResearch.com Interview with:
Howard S. Hochster, MD

Associate Director, Yale Cancer Center
Professor of Medicine, Yale School of Medicine
New Haven, CT 06520

Medical Research: What is the background for this study? What are the main findings?

Dr. Hochster: TAS-102 is a novel anti-metabolite, recently combined with a metabolic inhibitor to make it orally bioavailable and active in the treatment of cancer.  In pre-clinical studies, it is non-cross reactive with 5FU.  What this means practically is that we have another chemotherapy agent that can be used for patients with colon cancer.  This drug will be an addition to the approved chemotherapy agents 5FU, oxaliplatin and irinotecan.  It may be combinable with these and with targeted agents to provide new active regimens.

The main findings of the study were published in NEJM, May 15, 2015.  The study enrolled 800 patients randomized (2:1 ratio) to drug vs placebo.  Patients with advanced colon cancer who had been treated with all the previously approved drugs were eligible.  The drug was active in reducing time to tumor growth (Progression Free Survival) by 50% and improved overall survival for treated patients by about 25%.

The data I presented at ESMO included a further analysis on specific genomic subsets of patients within the 800 patient study.  All patients were tested locally for RAS mutations and about 50% had such mutations (as expected).  There was no differences in benefit or toxicity for those with RAS wild-type tumors or RAS mutated tumors.  We also looked at those with BRAF mutations, but only 15% of patients were tested and this mutation occurs in about 8% of colon cancer, so we had very few patients with BRAF mutation.  Given this limitation, it appeared that this did not make a difference for benefit or toxicity either.

Medical Research What should clinicians and patients take away from your report?

Dr. Hochster: TAS-102 is currently under review at the FDA and will receive a decision this year.  I expect it should be approved based on approval of other agents with similar benefits in such studies.  This will give patients a new therapeutic option after they have exhausted all others and possibly newer treatment options for earlier lines of therapy in the future.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Hochster: The next steps include combinations with irinotecan, with oxaliplatin and with biologics including bevacizumab.  These regimens can be eventually incorporated into the new treatment paradigms and guidelines.  We will be working on how this drug works after patients have been receiving 5FU and when tumors are resistant to 5FU.

Citation:

Presented at 2015

European Society for Medical Oncology | ESMO

Hochster H, Hager S, Pipas JM, et al. KRAS and BRAF gene subgroup analysis in the Phase 3 RECOURSE trial of TAS-102 versus placebo in patients with metastatic colorectal cancer. Ann Oncol. 2015;26 (suppl 4; O-010) – See more at: http://www.onclive.com/conference-coverage/2015-world-GI/improved-os-pfs-demonstrated-by-tas-102-regardless-of-kras-status#sthash.GYh8XDQX.dpuf

 

Howard S. Hochster, MD, & Associate Director, Yale Cancer Center (2015). Novel Anti-Metabolite Offers New Therapeutic Option For Resistant Colon Cancer 

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