Have you ever sat in a freezing cold scientific session and been so engrossed in the compelling presentations that followed, you simply forgot to take notes? Not one. That actually happened to me at the American Association for Cancer Research (AACR) in Philadelphia this year in one of the many fringe sessions that I attended.
Reading Terminal Clock, Philadelphia
Granted, the hot topic of the conference was undoubtedly checkpoint inhibition, but I was anxious to escape to the comfort of some meaty and familiar basic and translational science, namely MYC. MYC is largely thought to be a difficult to target, even undruggable protein, and along with RAS and p53, represents a formidable challenge for cancer researchers. These three oncogenic proteins alone are probably responsible for more drug resistance developing and even death from cancer than any other proteins in a patient with advanced disease.
For cancer patients with advanced disease, the clock is ticking on time they have left.
Solve these three problems (MYC, RAS and p53) and we may have a shot at dramatically improving outcomes. As Dr Gerard Evans (Cambridge) noted:
“I think it’s fair to say that we don’t really know why interruption of any oncogenic signal actually kills cancer cells, but one of the reasons that we’re interested in MYC is because it seems to be a common downstream effector of many, maybe all cancers.”
Sure, the road to success is paved with an enormous graveyard of failures, just as metastatic melanoma was before checkpoint blockade came along, ironically. What I heard at AACR both inspired and filled me with greater confidence… we’re finally getting somewhere.
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Multiple myeloma (MM) has been very much in the news this week after the American Society of Clinical Oncology (ASCO) abstracts were released to much anticipation.
Myeloma is largely thought to be an incurable disease despite the option of an autologous stem cell transplant for newly diagnosed patients. That said, I have actually met some people who have had two or 3 transplants over several decades, a testament to their strength and fortitude in enduring such a challenging procedure.
This year, the news media have focused on elotuzumab (BMS/AbbVie), a CS1/SLAMF7 inhibitor that has previously shown clinical activity in earlier trials, after it was showcased in the ASCO Presscast last week. This why you see many articles on the data reported from this particular abstract.
It’s not the most exciting new data in this disease for me though, that honour goes to two other therapeutics of an entirely different kind. They come completely out of left field and what we saw over the last two months really caught our attention and may surprise you too.
Indeed, we saw hints of some of this data at the American Society for Gene and Cell Therapy (ASGCT) meeting last week in New Orleans.
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The annual meeting of the 2015 American Urological Assoication (AUA) is being held in New Orleans… Yes, we’re on the third and final leg of our Louisiana trip encompassing AAI, ASGCT and now the triumvirate of AUA-SBUR-SUO.
This morning, I attended the Urologic Oncology Research Symposium, “High impact science in urologic oncology and progress in biomedical imaging.” In particular, I was keen to hear about the latest research in urothelial bladder cancer (UBC) with regards to checkpoint blockade with anti-PDL1 and PD-1 therapies.
In the past, any session on bladder cancer guaranteed the lucky (or hapless) presenters with an audience of a dozen or so people. Not any more – the room was packed with standing room only very quickly – a nice change for a disease that has seen no new therapies for 30 years.
Part of this renewed enthusiasm is due to the excitement for the checkpoint therapies making a huge impact in this disease, at least in clinical trials to date. While waiting for the session to start, one urologist I spoke to told me he bought the ASCO Virtual Meeting last year just to hear Dr Tom Powles talk on anti-PDL1 therapy with MPDL3280A in advanced urothelial cancer. What did you think of it, I asked?
“Wow, just wow!”
Later this month an update on the more mature data from that phase I trial is due at the American Society of Clinical Oncology (ASCO) from Dr Daniel Petrylak (Yale)… who just happened to be one of the presenters at AUA this morning.
He discussed the checkpoint data with atezolizumab (MPDL3280A) in urothelial bladder cancer, as well as the pembrolizumab data from ESMO last fall and what’s happening with nivolumab. These drugs are quite different in many ways, not just in terms of the efficacy, but also in terms of the biomarker data, as we discovered today.
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Whew, after posting the interview with Dr Tom Gajewski this morning from the American Association of Immunologists (AAI), we headed across town to the American Society for Gene and Cell Therapy (ASGCT) morning session and then dashed back to complete the first of the American Society of Clinical Oncology (ASCO) Previews for 2015!
What a busy week it’s been, never mind the hurly burly of today.
The ASCO 2015 abstracts went live at 5pm ET, with the exception of the late breaking abstracts, which are usually embargoed to the day of the actual presentation.
There are a number of topics well worth highlighting this year, so today kicks off the first of our annual Preview series on BSB. There will be much more to come – we wrote nearly 30 articles before, during and after the conference last year – this year will probably be similar with so much data to review and discuss.
As we wrap up our AACR coverage, I can’t believe it’s already time to discuss the annual American Society of Clinical Oncology (ASCO) meeting already – it seems to come around way too fast.
Over the last few years, we’ve reported on the rapid and impressive rise of innate, adoptive and adaptive immunotherapies in cancer research and wondered how long it would take before we see such data presented in the plenary session. That actually happens this year… finally!
A checkpoint trial makes the ASCO 2015 Plenary!
It does look like 2015 is the year that checkpoint inhibitors cannot be ignored for plenary selection with the wealth at data available at first AACR and now ASCO emerging.
This is no bad thing, especially given these drugs can affect the long tail of survival and are really starting to impact the dismal 5-year survival rates in metastatic melanoma and non-small cell lung cancer (NSCLC).
Beyond those two tumour types, what else can we expect to see and how is the data likely to shape up? We took a look at the abstracts available based on the titles only, the actual abstracts themselves come out next week.
What did we find?
You can check out our first Preview on the Top 10 immunotherapy trials with checkpoint blockade by signing up or logging in the box below…
We know from preclinical research that immunosuppressive tumour microenvironments can restrain anti-tumour immunity, thereby making subsequent therapeutic interventions less effective than expected. CD40 activation has been shown to reverse immune suppression and drive antitumor T cell responses, which in turn could lead to potentially better outcomes.
What happens when patients with advanced melanoma are given a checkpoint inhibitor plus an immune agonist such as anti-CD40?
Can we help the non-responding patients to checkpoint blockade improve their outcomes and shift the long tail in survival curves up using this approach?
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After yesterdays post on Gems from the Poster Halls at the American Association for Cancer Research (AACR) in Philadelphia where we took a look at new developments in targeted therapies, several subscribers asked for a repeat, but with a focus on immuno-oncology.
There are a number of elements that many people are interested in, especially given the Merck and BMS clinical data at AACR, where we clearly saw that:
- Anti-PD–1 therapy with pembrolizumab is superior to anti-CTLA4 with ipilimumab in metastatic melanoma (expect nivolumab to show the same thing at ASCO)
- Combined PD–1 plus CTLA4 blockade (with nivolumab plus ipilimumab) was superior to anti-CTLA4 alone, but with higher grade 3/4 toxicities, also in advanced melanoma
Sadly though, we still see that 70-80% of patients don’t respond to these therapies.
- How can we improve on that?
- What happens when we explore other factors, tumour types and different aspects of the immune system?
- What can we learn about novel sequencing or combination approaches?
- Which ones look interesting?
Endless questions can be asked – to which we still have too few answers – although there were some encouraging signs and hints of possibilities at AACR.
The 2015 AACR program was particularly challenging this year with lots of really good symposia and general sessions, making it tough to whizz round the vast poster hall spread out around the exhibits as well. To give you an idea of scale, it was pretty typical to cover 17K to 18K steps a day, approximately 7 to 8 miles. For many people, fitting in a quick lunch and the posters was certainly a challenging feat, depending where you were in the complex. With a morning session ending at 12.30pm, the afternoon session starting at 1pm and 2,000 steps between the Grand and Terrace Ballrooms, you sure had to get your skates on, Beep Beep!
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With the sheer breadth and depth of immuno-oncology data being presented at even the American Association for Cancer Research (AACR), several readers were prompted to write in and ask:
“Is this the end of the road for TKI therapies? Should we even bother to continue working on these agents?”
There was actually quite a bit of interesting data on regular novel targeted therapy to discuss, although I do concede that much of the mass media news focusing on the immuno-oncology tsunami in Philadelphia effectively drowned out targeted therapies and the results coming out in that space.
To maintain the balance between novel targeted agents and immunotherapy, here’s a review of some of the interesting new developments that I came across at AACR, from both the poster halls, as well as some of the thought leaders in this space.
When you stack up the emerging evidence in several tumour subsets, there are quite a few tasty morsels that are worthy of further discussion!
I’d like to take this opportunity to extend a warm welcome to all the new subscribers who took advantage of the AACR Special Offer to continue their education and learning about the exciting new developments in cancer research. Thank you for joining our conference coverage service, we really appreciate it.
To learn more about the hot topics in targeted therapies for cancer research, you can log in or sign up in the box below. Read on…
One of the obvious learnings from the American Association of Clinical Research (AACR) meeting earlier this week was that we are coming to the end of the low hanging fruit opportunities for checkpoint inhibitors as monotherapies.
Speaking with numerous company people in this space, there was wide consensus on that point. As one clinical lead put it succinctly, “From here on out, it’s going to get way more complicated – had a low grade headache develop after the very first science session I attended – and it’s still there after two days!”
How many of us know that feeling all too well? AACR always has the heaviest science load of any cancer conference we attend each year. Sure there’s some nice clinical data, but that is like nibbling on the light appetizers before the 20 course banquet. You need much stamina and fortitude to survive the brain fog at AACR. Then there’s the glee at snagging some key poster handouts at the meeting, only to be rapidly diminished when you try to read the 4pt print post hoc and realise your eyes cannot focus easily.
Looking at the long list of topics I want to cover in the in-depth post meeting analysis for a ‘lighter’ post, especially given that it’s Friday after a very long week, that sinking feeling hit home hard – there are no lightweight topics at AACR.
The other day, we posted about the promising data in triple negative breast cancer (TNBC), following on from the Genentech and Merck presentations at the San Antonio Breast Cancer Symposium (SABCS). These data surprised many folks, mostly because they didn’t consider breast cancer to be an immunogenic tumour – nor is lung cancer in the broader scheme of things for that matter – yet we are seeing some nice durable responses in both tumour types with checkpoint inhibitors.
In other words, our definition and perceptions must change as we redefine how we identify and think of possible ‘responsive’ cancers to these agents.
So where are likely heading next?
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Quick Reminder: Today is the last day for the AACR Special – the discount ends at midnight ET tonight. We may not offer this rate again as it’s a limited time only deal!
With the news hot off the press at the 2015 annual meeting of the American Association for Cancer Research (AACR) that Merck’s pembrolizumab (Keytruda) beat out BMS’s ipilimumab (Yervoy) in advanced melanoma, quite a few readers wrote in asking whether this signals the end for ipilimumab?
The short answer is no, and here’s why…
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