It’s been very clear for over four years now that combinations were going to be necessary if we want to a larger number of deeper and more durable responses than can attained with monotherapy. Gradually, we are starting to see early and very preliminary readouts with some of the trials in progress.
We are also learning very quickly that it’s going to be a case of #notalltumours and #notallsubsets.
Another very busy poster session at #ASCO16!
By this, I mean we obviously can’t take a one-combination-fits-all approach for all tumour types.
We need to be able to classify patients into more homogenous subsets and then devise different combinations or even sequences that address the underlying biology of both the cancer itself and also the tumour microenvironment. That’s going to take a while to sort out, perhaps even years.
Let’s not forget though that in the meantime, we can gather information quite a few clues both preclinically, as well as from initial clinical studies. Sometimes, after all, we even learn more from negative trials than positive ones. This is an area that is ripe for combinations with traditional targeted therapies, the question is which ones are promising and why?
We took a look at the landscape in SCCH&N and how this might evolve over time in the medium term, with future opportunities, that can be explored in rational combination approaches.
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EBCC-10 Cancer Conference
Amsterdam: The 2016 European Breast Cancer Conference organised by the European CanCer Organization (ECCO) is underway (Twitter: #EBCC10 – it’s the 10th official one they have organised).
We thought it would be a good opportunity to take a break from our coverage of #BMTTandem16 to look at some of the posters that are of interest at the meeting.
As regular readers know, we spend a lot of time reading posters – it’s where we pick up new trends and early data. Most go unnoticed or unpublicised in press releases.
For this post, I’ve highlighted four posters that I’m quite interested in and that merit further discussion.
They range from basic and translational research to clinical new product development. By chance, they are evenly split between immunotherapy (PD-L1 and TILs) and acquired drug resistance to different targeted therapies.
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After an entertaining morning yesterday – two interviews completed and wrong conference centre visited (yes really, there’s always a first for everything!) by lunchtime, things thankfully settled down.
Friday, for the uninitiated, is company symposia day – the equivalent of ASCO’s Super Friday. I rarely attend these in Europe, as they are more about corporate messages than what I call “proper CME”, meaning scientific or clinical fair balance and independence. This is one area where Europe still has a-ways to catch up the US on.
Before anyone gives me a hard time on this, I’ll never forget a vendor telling me a couple of years ago that I would love a particular symposia as he had personally ‘supervised and written’ the slides for the event, thus ‘ensuring’ it would be excellent while persuading me to attend against my better judgment. Naturally, I hated it – too many company messages or perspectives, and not ones I agreed with either – and left early, sadly disappointed.
We did attend the first ECC Press Briefing Friday afternoon with Drs Sant, Chouieri and Sharma. The last two authors presented on the metastatic renal cell carcinoma (mRCC) data after initial therapy, which is being presented in the Presidential Symposium on Saturday morning. It was quite an eye opener in many ways, with some subtleties well worth exploring in additional analysis and discussion.
Beyond the obvious highlights of the day for Saturday (nivolumab and cabozantinib data in mRCC), the first official day here is pretty jam packed with lots of other data to ruminate over. Throughout the day, we’ll be adding additional notes, commentary and insights as the data emerges – and wifi permits.
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A decade or so ago, the annual conferences for the European Congress of Clinical Oncologists (ECCO) and European Society of Medical Oncologists (ESMO) were considered convenient dumping grounds for negative or failed trials. This was largely because they received much less attention than their big brother, the American Society of Clinical Oncology (ASCO).
In the last few years, this trend has shifted with excellent clincial and scientific data being presented at both meetings – they alternate as hosts each year – under the European Cancer Congress (ECC) umbrella.
Just to confuse a global audience long used to referring to the meetings as ESMO and ECCO, while the logical Twitter hashtag might appear to be #ESMO14 and #ECCO15, respectively, based on the standard nomenclature of conference acronym followed by the year, the vagaries of European politics mean we end up with… #ECC2015.
It will be interesting to see how they compete for attention because this hashtag signal will be dirty (more than one usage) and noisy (many disparate voices) with the European Curling Championship, a European Cheerleader Convention and another on e-cigarettes and vaping, all seemingly using the same moniker!
Still, what many readers are really eager to learn though, is this a great, middling, or poor year for exciting new data in the field of cancer research and what can we expect to hear about in Vienna later this month?
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New developments in renal cell carcinoma
Continuing our focus on genitourinary (GU) cancers this week, today we turn our focus from prostate cancer to renal cell carcinoma (RCC).
There were two important announcments on Monday this week relating to renal carcinoma.
Firstly, Exelixis announced positive top line data from a phase 3 pivotal trial of cabozantinib versus everolimus in relapsed metastatic renal cell carcinoma (METEOR). The study met the primary endpoint (i.e. significantly improved progression free survival) and the company revealed the following data:
- Cabozantinib reduced the risk of disease progression or death by 42%; Hazard Ratio = 0.58, (p < 0.0001) compared to everolimus
- Interim Analysis of OS demonstrated a trend in favour of cabozantinib; Hazard Ratio = 0.67, (p = 0.005) compared to everolimus
- Exelixis to complete US and EU regulatory filings in early 2016
Secondly, a press release from BMS highlighted the phase 3 CHECKMATE–025 trial comparing nivolumab to everolimus, also in relapsed metastatic RCC, where the independent Data Monitoring Committee recommended early stoppage on the basis of the primary endpoint (OS) being met. The company likely be seeking discussions with Health Authorities with a view to filing the data with the FDA and EMA.
There are some interesting points that fall out of these releases. To learn more, subscribers can log-in below or you can purchase a subscription in the box below.
At the last count, the renal cell carcinoma (RCC) space is quite competitive with five VEGF inhibitors (sunitinib, sorafenib, axitinib, pazopanib and bevacizumab), two mTOR blockers (temsirolimus and everolimus) and not forgetting IL–2, all approved by the FDA for the treatment of advanced disease.
Much of the recent focus has been on sequencing, exploring combinations (generally too toxic with little added benefit), and evaluating the potential for novel immunotherapies in development such as checkpoint inhibitors. Biomarkers are few and far between, making it hard to rationally decide which therapy each patient should get and in which sequence.
The key question is, why is this tumour type so challenging from a clinical and scientific perspective?
Recently, new data has begun to emerge that may help inform or enable us to switch to new approaches. While the urologists are eagerly watching the live surgery on the EAU cam, we highlight research data presented at the European Association of Urology (EAU) in Madrid and take a look at how the underlying biology of RCC can elevate our knowledge about where the potential future strategies and blueprint might lie, if we want to facilitate exciting new developments in this field.
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Yesterday, the European Society of Medical Oncology (ESMO) released the abstracts to the poster and poster discussion sessions. This preview will be quite long by nature of it being the first time we get a look at the topline details behind some of the key sessions and their abstracts for both immunotherapies (especially checkpoint inhibitors) and targeted therapies. This includes posters and their discussion sessions, plus poster late breaking poster titles.
For reference, you can find the ESMO 2014 poster and poster discussion abstracts can be found here.
In addition, there appears to be some pretty cool presentations in the Special Symposia, which are rather like ASCO scientific symposia and contain a lot of useful information and often strategic ideas about where thought leaders see hot topics going in the future. This can be very helpful in learning about possibilities for new clinical trials ahead of time. As we focus on the poster highlights today, do check back tomorrow for a detailed look at the scientific symposia.
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“You may say I’m a dreamer
But I’m not the only one.”
John Lennon, Imagine
As part of our ongoing series on the AACR Previews, today I want to take a closer look at some interesting scientific and clinical data in triple negative breast cancer (TNBC). One reason for this is that we need to remember that the disease, as currently defined, is essentially what’s left after taking out the ER+, HER2+ and inflammatory breast cancer subsets. In other words, it’s a very heterogeneous catch-all population, making clinical trials rather challenging at best. It also means that the chances of success in general all-comer trials is rather low.
It is my hope that as we learn more about the biology of this disease, we may see further subsets be defined by molecular peculiarities, much in the same way that gastrointestinal stromal tumours (GIST) were defined by KIT expression and CD117. Once we have more homogenous subsets, it will be easier to conduct trials just looking at those specific patients, thereby improving the chances of clinical success with therapeutic intervention.
There’s been a lot of work focused on this area over the last few years, so it seems a good point to find out where the progress has got to.
Without much further ado, what can we learn about the biology of TNBC from AACR this year and which potential new targets might emerge?
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Following on from yesterday’s post on the potential for small basket trials in ER+ breast cancer with the ESR1 mutation, I wanted to highlight another area where these type of highly focused and rational studies appear to be not only useful but also potentially produce stunning responses.
Some of you will recall the fascinating and widely told story of a single bladder cancer patient at Memorial Sloan Kettering who was resistant to multiple lines of therapies. The team sequenced the genome and found a rare TSC1 mutation. Importantly, this is known from pediatric astrocytoma studies, to be sensitive to an mTOR inhibitor, everolimus (Afinitor). The refractory patient was given the drug and responded well. The rest is history, as they say.
Can we learn more from these type of appraches, i.e. genomic sequencing of patients who have relapsed after initial therapy?
Can we also learn more from the few exceptional responders in clinical trials – what was unique about their response that elicited such a stunning effect?
The short answer is a resounding yes – to learn more about some stunning new genomic approaches to research and the lessons we can learn for future drug development, sign in or sign up below.
It’s been a long 14+ hours here on the first day of ECCO in Amsterdam and I’m starting to flag