Continuing part two of our mini-series on colorectal cancer, today we move from the big scale Immunoscore study to small subsets of disease that are looking interesting in several ways.
For years, advanced colorectal cancer has been dominated by chemotherapy (FOLFOX or FOLFIRI) with and without targeted therapies (VEGF and EGFR antibodies), with very little new to talk about. Part of the challenge here is how do you add something the existing standard of care and move the needle significantly. In front-line, for example, the OS is already out 2-plus years, so these are long and risky trials to undertake. Not surpisingly, many companies have sought to evaluate their agents in tumour types where they consider the risk of development to be lower.
Unless… we can find creative approaches that turn the paradigm on its head and identify a clearly defined niche that can be carved out separately from allcomers.
This is where we’re at now – identifying subsets that might respond exquisitely to novel approaches based on a rational understanding of the underlying biology. One obvious subset might be BRAF, which can be treated with a BRAF inhibitor with or without other targeted therapies as Dr Pietrantonio and colleagues (2016) literally just showed for example, but what about others of potential interest?
Colorectal cancer with microsatellite stable (MSS) disease represents 95% of metastatic patients. These are people whose mismatched repair system is proficient and actively functional in fixing the DNA strand breaks that occur during the course of life.
In contrast, those with microsatellite instability (MSI) are the minority of people with colon cancer (and some other cancers too) whose mismatched repair system is deficient and unable to adequately repair the DNA strand breaks. Ironically, this leads to thousands of mutations that can be recognised by the immune system to help detect the presence of cancer. It also tends to occur in hereditary cancers such as Lynch Syndrome.
We’ve been following the MSI vs MSS story for a while now, but at ASCO this year there was more data available and things appear to be getting clearer on the commercial front too.
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We’ve been following the work of Dr Jérôme Galon, a French immunologist, on Immunoscore for a while now, and many readers will remember the last interview he kindly gave BSB from the European Cancer Conference in September [Link].
In 2015 the large global trial to validate Immunoscore as a biomarker was still ongoing, so if you want some background to this important concept, do check out Dr Galon’s interview as it’s well worth reading as a primer on immunosurveillance, the importance of immune cells – the type, density and location, as well as background on the Immunoscore test as a marker of outcome.
Since then, the group have also published some related data that both moves the field forward and offers a way to unify some important concepts in colorectal cancer.
In Chicago, the really good news was that the final results of a large global study involving nearly 4,000 patients were presented to a packed audience in the main hall where the plenary is held. It’s not often you see the gastrointestinal oral session allocated the prime time room over lung or breast cancers – the atmosphere was certainly electric with anticipation!
This week’s post ASCO mini series focuses on colorectal cancer, with a look at several important aspects of this disease as we learn more about the underlying biology, as well as how the immune system functions and how we can use that scientific knowledge to improve outcomes for patients, sometimes in a dramatic way.
To learn more about these promising new developments and read what Dr Galon had to say, subscribers can log-in.
Chicago – it’s “Plenary Sunday” at the 2016 annual meeting of the American Society for Clinical Oncology (ASCO).
Cancer immunotherapy has arrived at ASCO! Not so long ago cancer immunotherapy presentations were in small meeting rooms and had only a few attendees – at this meeting cancer immunotherapy data is being presented to thousands of attendees in large meetings rooms, including the B1 plenary hall. What a difference in the space of a few years!
Today at ASCO there are several noteworthy cancer immunotherapy presentations. We’ll be writing about them here on the blog during the day.
Part of the opportunity of coming to a meeting such as ASCO is the networking opportunities it affords.
While in Chicago I heard about a phase 3 trial from a global pharma company that failed to meet its primary endpoint last year, however, – to the best of my knowledge – there’s been no publication or presentation of the negative data that may help the field move forward. The investigators have been told “it’s a bust.”
Not to publish or present negative data is a disservice to the patients that enrolled on the trial. Many would have believed their participation would contribute to the advancement of science and medicine, and potentially benefit others.
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Update 12.30pm. Occasionally we decide something we talk about needs to be “open access” so we’ve published a short post. It is freely available to all. Turns out the negative data from BMS was mentioned in a July 23, 2015 financial results press release. Almost a year later, the negative data has still not been presented or published.