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Posts from the ‘Prostate Cancer’ category

Dr James Gulley is Chief of the Genito-Urinary malignancies branch and Director of the Medical Oncology service at the National Cancer Institute (NCI) in the National Institutes of Health. He’s a world-leading GU cancer expert and at the forefront of pioneering research to make cancer immunotherapy work in prostate cancer.

We last spoke to him at ASCO 2015 (See post: The future of prostate cancer immunotherapy). You can listen to excerpts from this interview on Episode 4 of the Novel Targets podcast (See: The non-inflamed tumour show).

Almost two years on, and new research by Dr Gulley and colleagues from the NCI shows that the STING pathway may have an important role to play in prostate cancer immunotherapy. Activation of this pathway through a novel mechanism could turn a cold non-inflamed tumor into a more inflamed or hotter one in men with advanced prostate cancer. How cool is that?!

At the 2017 annual meeting of the American Association for Cancer Research (AACR) that was recently held in Washington DC, Dr Gulley graciously spoke to BSB about some of the novel trials that are underway at the NCI, with the aim of making cancer immunotherapy work in men with advanced prostate cancer.

Dr Jim Gulley, NCI at AACR17

This is the seventh expert interviews in our series from AACR17 where we explore the conundrum:

How does Dr Gulley plan to light the immune camp fire in prostate cancer?

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Lemons Villa BorgheseThe discovery of a novel target in castration-resistant prostate cancer (CRPC) and the potential of drugs targeting this to delay or overcome adaptive resistance is the subject of today’s post.

Followers of the prostate cancer field know that one of the challenges with drugs such as enzalutamide and abiraterone is that patients stop responding to them over time and they develop acquired resistance.

So imagine that you could give a drug that is not only an effective anti-cancer agent in patients with acquired resistance, but might then allow those treatments to be effective a second time around.  A recently identified druggable target means this is now a possibility.

Of course, it’s early days yet, and the preclinical work has yet to translate into humans, but it’s not hard to see the commercial implications in the prostate cancer landscape for companies such as $MDVN, $JNJ, $TKAI, Bayer and anybody else who wants to be a player.

Interested? Subscribers can login to read more or you can purchase access. This post is Day 3 in our Road to AACR 2016 series.

San Francisco Cable CarWe’re continuing our post-meeting coverage of the 2016 Genitourinary Cancers Symposium (ASCO GU) that took place earlier this month in San Francisco.

In this post we’re taking a look at the results of a clinical trial with a non-invasive liquid biopsy which in a cohort of patients with prostate cancer identified increased risk of death on abiraterone and enzalutamide, but not taxane chemotherapy.

What struck me listening to this presentation was the simple elegance of an approach, which the presenter likened to the equivalent of “facial recognition” of prostate cancer cells.

As the ASCO GU discussant noted, this could have an impact on clinical trial design, potentially leading to more rapid prostate cancer drug approvals.

Subscribers can login to read more about a biomarker approach, that if validated in a prospective trial, could help identify the optimal sequencing of prostate cancer drugs for patients.

Alcatraz San FranciscoIn yesterday’s post on novel targets in advanced prostate cancer, we looked at a potential new concept that is emerging and being evaluated in clinical trials.

Today, we continue that approach with a look at another novel – and quite different target – as well as ways of repurposing old drugs to help potentially overcome the drug resistance seen with newer therapies for this disease.

Warning: the concepts discussed here may well take you by surprise, although they are based on rational and logical evidence from recent scientific research.

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Coit Tower San FranciscoAt the recent ASCO 2016 Genitourinary Cancers Symposium (ASCO GU) that took place in San Francisco the week before the JP Morgan Healthcare Conference (JPM), one of the noteworthy presentations was on a novel target for men with advanced prostate cancer.

While JPM may have been a “dud” for many, several companies did take the opportunity to update and discuss their corporate strategy going into 2016, which gave a surprising amount to comment on in our 3 blog posts from the meeting: JPM Day 1, JPM Day 2, JPM Day 3.

In this post we look at the “take homes” from the ASCO GU presentation, and what looks like it could be a new race to market.

It’s good to see novel targets for men with advanced prostate cancer, and potential new treatment options on the horizon!

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Immune checkpoint inhibitors that target CTLA4, PD1 and PDL1 can generate prolonged responses in a minority of patients, but the results so far in prostate cancer have been disappointing. Prostate cancer doctors have not been part of the excitement spreading through the cancer community like a “Mexican wave.”

Prostate cancer has not featured significantly in the cancer immunotherapy news recently, but that’s not to say there is not a lot going on. The phase 3 trial results of ipilimumab (a checkpoint inhibitor of CTLA-4) in the pre-chemotherapy setting of advanced prostate cancer (NCT01057810) are expected soon and there is also the eagerly awaited phase 3 trial of the PROSTVAC vaccine (NCT01322490).

Dr James Gulley ASCO 2015

At ASCO 2015, BSB interviewed Dr James L. Gulley, MD, PhD Chief of the Genitourinary Malignancies Branch and Director of the Medical Oncology Service at the National Cancer Institute (pictured above).

He talked about some of the cancer vaccine work he has done as part of the CRADA (Cooperative Research and Development Agreement) between the NCI and Bavarian Nordic, as well as strategies to help immunotherapy work in those tumors such as prostate cancer that are non-inflamed, where there may be an insufficient immune response for checkpoint inhibitors to work effectively.

Readers may recall we interviewed him at ASCO GU earlier year, “How to make non-immunogenic cancer sensitive to checkpoint inhibitors.” His outstanding work could shape the future of prostate cancer immunotherapy.

This post also includes additional ASCO 2015 commentary on from Dr Oliver Sartor, Professor of Cancer Research at Tulane University, who shared his perspective on the ipilimumab and PROSTVAC phase 3 prostate cancer trials that are due to readout soon.

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Medivation-LogoNew Orleans – in today’s plenary session at the 2015 annual meeting of the American Urological Association (Twitter: #AUA15), Dr Celestia Higano (Seattle), presented the results of the STRIVE trial (NCT01664923) – a multicenter phase 2 study of enzalutamide (Xtandi) versus bicalutamide in men with nonmetastatic (M0) or metastatic castration-resistant prostate cancer (M1). These were men who were asymptomatic or mildly symptomatic.

Dr Celestia Higano STRIVE AUA 2015

Dr Higano noted that this was a very late breaking abstract; topline results were only announced a little over a month ago on April 2.

The TERRAIN trial also compared the efficacy of enzalutamide head-to-head against bicalutamide. We’ve updated our EAU 2015 TERRAIN post with the additional data presented here at AUA 2015 in New Orleans.

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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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EAU 2015 LogoMadrid, Spain – the results of the Medivation/Astellas TERRAIN clinical trial of enzalutamide (Xtandi) versus bicalutamide (Casodex) in men with metastatic castration resistant prostate cancer (mCRPC) were presented today at the European Association of Urology Congress in Madrid (Twitter #EAU15).

Professor Dr. med. Axel Heidenreich. Credit: Universitätsklinikum Aachen

Credit: Universitätsklinikum Aachen

The clinical trial data were presented in a plenary session at EAU15 by Axel Heidenreich (pictured left) who is Professor of Urology & Uro-oncology at the RWTH University and Head of Department & Director of the Urology Program at the University Hospital in Aachen, Germany.

How good are the results, and what impact will they have on the prostate cancer treatment landscape in Europe? Prof Heidenreich kindly spoke with Biotech Strategy Blog (BSB) and shared his thoughts.

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Update May 17, 2015: This post has been updated with the additional TERRAIN trial data presented by Professor Arnauld Villers (Lille) at the 2015 annual meeting of the American Urological Association (AUA) in New Orleans.

Prof Arnauld Villers presents TERRAIN trial data at AUA 2015

Prof Arnauld Villers presents TERRAIN trial data at AUA 2015

We have been following the results of the checkpoint inhibitors for several years now, first with ipilimumab (Yervoy) and lately with anti-PD1 and PD-L1 inhibitors such as nivolumab, pembrolizumab and MPDL3280A. Irrespective of the antibody used, the best results we’ve seen have in melanoma, lung and bladder, but some tumour types such as colon and prostate cancers have barely been responsive at all.

Why is that?

Can we find ways to make non-responsive solid tumours responsive to immune therapies, and if so, what strategies could we employ to enable improved responses and outcomes?

At the ASCO Genitourinary (GU) meeting in Orlando this weekend there were some interesting hints of what might be possible in the not too distant future.

To learn more about this phenomenon, we conducted an interview with a leading cancer immunologist to find out what they are doing to make a difference in the GU space.

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