Cancer genetic mutations not all treatable: System to rank relevance of mutations needed

Lugano, Switzerland, April 11, 2018 – ESMO, the leading professional organisation for medical oncology, welcomes the latest reports from The Cancer Genome Atlas (TCGA) as a major resource for researchers across the world and calls for increased across-the-board commitment to translate these efforts into medical advances for the benefit of cancer patients. The TCGA collaboration conducted genome analysis, called the Pan-Cancer Atlas, on more than 10,000 tumours from 33 types of cancer and published 29 papers. (1)

"The studies highlight genomic alterations in cancer tissue, but while it is tempting to believe that they are all important, sometimes giving a drug matched to the mutation does not benefit patients," said Prof. Fabrice André, Professor in the Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France, Chair of the ESMO Translational Research and Personalised Medicine Working Group, (2) Editor-in-Chief of ESMO's flagship journal Annals of Oncology, (3) and Co-Chair of the ESMO Molecular Analysis for Personalised therapy (MAP) congress. (4)

"Large-scale clinical trials are now needed to determine which alterations can be treated and are therefore relevant from a medical perspective," he continued. "Cancer geneticists have done an incredible job identifying the mutations; now oncologists and the broader oncology community must take the lead and find out which mutations can be targeted to treat patients."

André said that genomic alterations should now be ranked according to whether or not they can be treated. "This will avoid confusion between actionable alterations and alterations that are not medically relevant and therefore won't translate into a benefit for patients. ESMO is currently devising a uniform ranking system which will help oncologists interpret data and explain the consequences to patients."

The TCGA research confirms that some genomic alterations are shared across tumour types and suggests that cancer should be classified by these alterations, rather than the tissue of origin. For example, some mutational processes are shared across tumour types and could define subsets of patients eligible for targeted therapies or immunotherapy. "As reported previously, in rare cancers that share genomic alterations it may be time to seek pan-cancer registration for drugs," said André. (5,6) "But for some other cancers it is too early to adopt this approach. We know that treating a certain mutation benefits patients with some types of cancer but has no impact on other types of cancer."

"The TCGA project has been a massive investment that has shed light on cancer genomics. It is now time to translate these research findings into medical advances, and to achieve this, similar investment is needed in clinical research."

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References

1 Pan-Cancer Atlas: http://www.cell.com/pb-assets/consortium/pancanceratlas/pancan/index.html

2 http://www.esmo.org/About-Us/Who-We-Are/Educational-Committee/Translational-Research-and-Personalised-Medicine-Working-Group?hit=mag

3 https://academic.oup.com/annonc/pages/About

4 http://www.esmo.org/Conferences/MAP-2018-Molecular-Analysis-for-Personalised-Therapy

5 Drilon A, Laetsch TW, Kummar S, et al. Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. N Engl J Med. 2018;378(8):731-739. doi: 10.1056/NEJMoa1714448.

6 André F. Developing Anticancer Drugs in Orphan Molecular Entities – A Paradigm under Construction. N Engl J Med. 2018;378(8):763-765. doi: 10.1056/NEJMe1716821.

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