Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘abiraterone’

westminster-embankmentToday’s news that an FDA Oncologic Drugs Advisory Committee (ODAC) review will not be required for rucaparib is good news for Clovis Oncology. The company announced this via an SEC 8K filing:

“The Food and Drug Administration (“FDA”) has notified Clovis Oncology, Inc. that FDA is not currently planning to hold an advisory committee meeting to discuss the Company’s New Drug Application for rucaparib.”

However, given the unmet medical need in ovarian cancer, a lot of companies are targeting both platinum sensitive and platinum resistant disease.

In our fourth preview of the forthcoming European Society for Medical Oncology (#ESMO16) meeting we’re looking at 9 key ovarian cancer abstracts to watch out for at ESMO.

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PREVAIL trial EAU 2015We’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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After the intensity of gastrointestinal cancer, we now turn our attention to genitourinary (GU) cancers with the upcoming ASCO GU meeting later this week in Orlando.

Two of the big topics here will be prostate and renal cell (RCC) cancers.

Unfortunately, the long awaited data in adjuvant RCC demonstrated that early treatment with sorafenib or sunitinib did not improve outcomes in locally advanced kidney cancer after resection. According to the ASCO press release, the trial conducted by Dr Haas and colleagues at U Penn discovered that:

“The average period to disease recurrence was similar between those who received sorafenib or sunitinib after surgery (5.6 years) and those treated with placebo (5.7 years).”

We will therefore turn our attention to castration resistant prostate cancer (CRPC).

One of the recent and ongoing controversies is splice variants, especially AR-V7, which is thought by some research groups to confer resistance to the hormonal therapies, enzalutamide and abiraterone. The big question though, is does it, and how useful is an assay in helping to determine appropriate therapy? Are there other factors at play?

We looked at the latest data and put the findings in context with what we know from other published research.

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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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We hope that everyone had a relaxing holiday break and now it’s time to get back to work.  Tomorrow I will review some more of my thoughts in the immuno-oncology space, since that area had a tremendous amount of progress in San Diego with lots of new ideas to process and summarise.

In the meantime, a few people have written in and asked about what was happening with overcoming resistance in various tumour types, was there anything new to say in that space that was in addition to the the detailed previews we covered before the conference?

Actually, there was a quite a few posters and presentations that caught my eye, so I thought this would be a good idea to review them here:

Lung Cancer: HER2, VEGF, T790M, EGFR, erlotinib, gefitinib, trastuzumab, bevacizumab, CO-1686, AZD9291

Prostate Cancer: mTOR, PI3K, Androgen Receptor, enzalutamide, abiraterone, CC214–2, ARN–509, BET Bromodomian inhibition, ODM–201, GDC–0980, GDC-0068, PF–04691502, BKM120, BEZ235

This week we turn our focus to the American Society of Clinical Oncology Genitourinary (ASCO GU) symposium being held in San Francisco.

The hottest topic is highly likely to be the Medivation and Astellas data for enzalutamide (Xtandi) in the pre-chemotherapy setting in men with advanced prostate cancer who are asymptomatic or slightly symptomatic and naive to chemotherapy.  Previously, I wrote in detail about the Medivation announcement regarding the interim analysis where the PREVAIL trial was found to meet its primary endpoint (open access).

Dr Tom Beer, OHSU

Dr Tom Beer, OHSU

The company subsequently stated that the data had been accepted as a late breaker for the the ASCO Genitourinary meeting in San Francisco this weekend.  That data is being presented on Thursday morning in the oral prostate cancer session by Dr Tomasz Beer (OHSU), who is the Deputy Director of the Knight Cancer Institute and a prostate cancer specialist.

The ASCO GU 2014 abstracts will be available for perusing as of 5pm ET today.

This week I caught up with Dr Beer to discuss not only the details relating to the PREVAIL data, but also how enzalutamide (Xtandi) potentially fits in the advanced prostate cancer competitive landscape given that he also participated in the abiraterone (Zytiga) COU-AA-302 trial in the same clinical setting.

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I am off to Washington DC tomorrow for the annual meeting of the American Urological Association (AUA).

If you are not able to attend, then you can follow the Twitter coverage on Pharma Strategy Blog where Sally Church (@MaverickNY) will be aggregating the tweets.  The conference hashtag is #AUA2011.  I also expect to be live-tweeting from the conference.

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Like many medical conferences in the United States, the AUA meeting kicks off with independent continuing medical education (CME) satellite symposia on topics of interest.

As a lawyer who has to pay for his own continuing legal education (CLE) credits, I have to confess that I am somewhat cynical that other professionals such as physicians expect to have their CME paid for through free industry-sponsored events.  These symposia are certainly not cheap to run.

However, compared with Europe, CME events in the United States are usually well-produced and fair balanced, albeit with a topical theme that obviously relates to the sponsor’s interest.

The two satellite symposia that I will be attending at AUA are Friday evening’s Amgen supported “Managing Skeletal-Related Events in Patients with Prostate Cancer” and the Saturday morning Astellas/Medivation supported “Reason for Hope: Key Advances in the Management of Castration-Resistant Prostate Cancer.”

While at Quintiles, I was lead CRA/European Project Manager for the phase III trial trial of risedronate in elderly women at risk of hip fracture, so I am interested in bone related treatments, and am looking forward to hearing more about denosumab (Xgeva®) and its impact on skeletal related events (SRE).

Oliver Sartor (Tulane) raises some excellent questions in a recent paper published in the Asian Journal of Andrology, “if a patient has a SRE, does it affect the way a patient feels, functions or survives?”

Sartor argues that a better definition of the benefit a drug has on SRE’s would be “a reduction in pain, analgesic consumption or improvement in quality of life (QoL)” instead of the current “feel, function or survive” standard.

He notes that patients with bone-metastatic castrate resistant prostate cancer (CRPC) have a limited life expectancy, so that QoL is a key issue. “An asymptomatic event linked to a future adverse event is less meaningful in a patient with metastatic CRPC.

Sartor concluded his paper by saying:

“The lack of effect of bisphosphonates or denosumab on patient-reported outcomes including QoL, pain or analgesic consumption continues to be a disappointment for this entire field.”

When we talk about a reduction in SRE’s what does this really mean for the patient?  I look forward to hearing what the expert panel at Friday evening’s symposia on this topic and hope it will be addressed.

Moving on to the other satellite symposium, supported by Medivation/Astellas, that I will be attending early on Saturday morning.  I expect this symposium will focus on new drugs in the pipeline such as MDV3011 and ARN-509 that target the androgen receptor. Hopefully they will also discuss other therapeutics, such as the recently approved abiraterone acetate (Zytiga®), as well TAK-700, which has a similar mechanism of action to abiraterone, i.e. they both inhibit CYP17 and testosterone production.

I’m looking forward to hearing what the expert panel has to say about the need to take prednisone with abiraterone, and whether there are any issues surrounding long-term usage if abiraterone ends up being used earlier in the pre-chemotherapy setting.  Updated data from the COU-AA-301 trial will be presented at AUA on Monday, and I expect a lot of interest from urologists in this.

The satellite symposia are set to be a good warm up act to the start of the main AUA meeting that runs from May 14 to 19 in Washington DC.  I’ll be writing more from the AUA 2011 over the next few days.

ResearchBlogging.orgSartor, O. (2011). Denosumab in bone-metastatic prostate cancer: known effects on skeletal-related events but unknown effects on quality of life Asian Journal of Andrology DOI: 10.1038/aja.2011.33

Today at the European Association of Urology (EAU) annual meeting in Vienna, the big news was that 2010 was a “Grand Cru” year for new treatments for advanced prostate cancer.  Not only that, but sanofi-aventis announced that they had received European marketing approval for cabazitaxel (Jevtana®) in metastatic hormone resistance prostate cancer mHRPC.

The fact that there are now several new treatments available (or expected to be available in the not too distant future) is good news for patients and physicians.

What is interesting about prostate cancer is that it in terms of incidence it is comparable to breast cancer, yet seems to end up with far fewer resources and publicity.  Prostate cancer is to men, what breast cancer is to women.

The EAU 2011 Congress website has a variety of podcasts and webcasts of presentations, and I encourage anyone interested in the latest developments to check out the wealth of information they offer.  In particular, the presentation by Professor Johann De Bono from the Royal Marsden in the high risk prostate cancer plenary session today was one of my highlights of the meeting.

The take home message I obtained from EAU in Vienna is the excitement of new treatment options for castration resistant prostate cancer (CRPC) such as cabazitaxel, sipuleucel-T and abiraterone.  The challenge may well be to work out how best to use these new therapies, ie in what sequence and what potential combinations may evolve in the future.

However, as Professor Bertrand Tombal from Louvain in Belgium declared, 2010 was a Grand Cru for new prostate cancer treatments.  That is good news indeed.


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