In today’s post, it’s time to address a bunch of questions we’ve received over the last few weeks from subscribers about the latest and – not so greatest – in cancer research.
ASCO 2015 Chicago
Sometimes these queries are fairly straightforward to answer, other times requires some sleuthing and hunting down thought leaders for some additional context and insights… For obvious reasons, these folks are best caught in person at cancer conferences such as AACR and ASCO. The feedback isn’t always sparkly and positive though, it can also be gloom and doom, just like the inclement weather!
So here goes, questions on the following are covered in the article below:
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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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We’ve been following the updates on the PREVAIL study evaluating enzalutamide (Xtandi) versus placebo in metastatic castrate-resistant prostate cancer (CRPC) in the pre-chemotherapy setting for a while now. It’s interesting to see how the data evolves over time as it becomes more mature.
The first presentation, back in January 2014 at ASCO GU by Dr Tom Beer (OHSU) reported on the first 540 deaths and was subsequently followed by an update of the survival data at AUA in May of the same year by Dr Chris Evans (UCLA).
This morning at the European Urology Association (EAU) in Madrid in the late breaking session on prostate cancer, the honour fell to Professor Bertrand Tombal (Leuven), who did a very nice job of reviewing the mature PREVAIL data (based on 765 deaths) and providing some context for how the CRPC landscape is being impacted by AR pathway inhibitors.
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It’s now time to turn our attention to genitourinary oncology and, in particular, prostate, renal and urothelial bladder cancers. This week brings this ASCO GU meeting (#GU15), which is being held in Orlando this year and began this morning.
There are quite a few interesting topics being covered here, particularly in the poster sessions over the next three days. Hopefully, 2015 will also bring more good news in this space as 2014 was a rather dismal one on several fronts!
We decided to highlight some of the most interesting abstracts on castrate resistant prostate cancer and urothelial bladder cancer in our latest conference preview.
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There’s nothing better than seeing good news in the early morning email alerts I have set up on cancer research!
Today, it was the turn of Astellas and Medivation to announce the results of the TERRAIN study, which is a primarily European phase 2 trial that began in March 2011 in the prechemotherapy setting for castrate resistant prostate cancer (CRPC). The trial met its primary endpoint of progression free survival (PFS).
Why is this an important landmark in CRPC and what does the initial data show?
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A lot has happened this month with San Antonio Breast Cancer Symposium (SABCS) and other data emerging that it could be subtitled:
A brief tale of two breast cancer drugs
At SABCS a couple of things looked pretty intriguing indeed. One we will cover in the New Year, along with an in-depth expert interview on the topic, while the other is the main focus of today’s note.
In the last post of 2014, it’s time to address some pertinent questions on triple negative breast cancer (TNBC) from subscribers – there is good news to report here, unlike the surprising MARIANNE results for Kadcyla and Perjeta in frontline HER2+ disease that were announced early this morning.
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A big thank you to all who have supported Biotech Strategy Blog Conference Coverage this past year. Wishing you good health, happiness and prosperity in 2015. See you on the other side!
This last week saw the ASCO Breast Cancer Symposium in San Francisco, although very little caught my attention from a drug development point of view. Much of the attention seemed to be focused on surgery, genetic counselling and screening.
With the 2014 European Society of Medical Oncology (ESMO) conference in Madrid coming up fast in only 2 weeks time, it seems a good point to take a look at what’s on the slate there, since there are some important clinical trials being presented there with new data that we can expect to hear a lot more about.
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Companies mentioned: Roche/Genentech, GSK, Novartis, AstraZeneca, Medivation, Astellas
Drugs mentioned: Pertuzumab, trastuzumab, lapatinib, PI3K inhibitors, olaparib, enzalutamide
There are a couple of important breast cancer trials with data being presented for the first time at Madrid.
At the ASCO GU meeting in January, Dr Thomas Beer presented the initial data for the PREVAIL trial, which explored enzalutamide (Xtandi) in castrate resistant prostate cancer (CRPC) prior to chemotherapy. Reactions to the data were mixed with many analysts, perhaps naively, focusing on the significant temporal survival benefit (2 months) rather than the 29% hazard ratio, which demonstrates the magnitude in the reduction in the risk of death over the control arm.
This weekend at the American Urological Association (AUA) meeting in Orlando, Dr Christopher Evans (UC Davis), presented the updated data, including the survival curves and a subset analysis for visceral and non-visceral disease. He focused on the clinical benefits that were clinically meaningful to the urology audience.
I have to say that the data shown was both compelling and impressive to me.
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Over the last few years we have seen new therapies emerge for the treatment of advanced prostate cancer from immunotherapy to chemotherapy and second generation hormone therapies. Each of these has increased survival and outcomes. Along the way though, a host of other agents have fallen by the wayside with a raft of negative phase III trials that did not live up to their phase II promise. These include atrensentan, dasatinib, ipilimumab, lenalidomide and more recently, custirsen.
Much of the focus has, however, been on the hormonal drugs, abiraterone (Zytiga) and enzalutamide (Xtandi) in both the pre and post chemotherapy settings. One thing has become clear though – over time the responses attentuate as resistance sets in. This is very common with oral therapies.
Some big questions to consider here are:
- What causes it?
- How can we overcome adaptive resistance?
- Would combination approaches produce synergistic results?
- Or should we consider new targets with a different mechanism of action (MOA)?
The answers to these questions are now being eagerly explored through basic, translational and clinical research. I was very impressed with the quality of research and breadth of fresh ideas and approaches emerging from the SBUR, SUO and UOR sessions at AUA this year, including new combination trials already in the planning phase.
In the past, Bertrand Tombal (Belgium) talked about the Grand Cru year for clinical research in CRPC. In the future we may well look back at 2014 as a similar Grand Cru year for basic research for prostate cancer, if the findings translate to clinic. The bench-to-bedside process is very much alive and well in urologic research.
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Since 2004, six new prostate cancer treatments have been approved for advanced prostate cancer: docetaxel (Taxotere), sipuleucel-T (Provenge), cabazitaxel (Jevtana), abiraterone (Zytiga), enzalutamide (Xtandi), radium-223 (Xofigo).
In the process, the competitive landscape has been radically transformed.
What we have seen more recently with the PREVAIL and COU-AA-302 data is a move to treat mildly symptomatic men earlier in metastatic disease prior to chemotherapy, thereby delaying disease progression, and in the case of enzalutamide, improving overall survival.
But how early can you go?
The focus of several companies looking to bring new prostate cancer drugs to market is now shifting from symptomatic metastatic castrate resistant prostate cancer (mCRPC) to earlier in the disease setting, i.e. asymptomatic M0 disease.
There are number of critical questions that need addressing, including:
- Should we treat men with metastatic (M0) castration-resistant prostate cancer (CRPC) who are asymptomatic?
- Will the treatments be able to demonstrate that taking them means men will live longer and feel better?
- Will there be a market for AR antagonists such as enzalutamide, ODM-201, and ARN-509 in M0 prostate cancer, where large randomised phase 3 trials are either underway or are planned?
Prof Tombal at ASCO GU 2013
During ASCO GU, I asked one of the leading thought leaders and researchers into this area for his candid perspective.
Subscribers to Premium Content can sign in or sign up in the box below to read what Professor Bertrand Tombal had to say on this topic – his answers may well surprise you.