Biotech Strategy Blog

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

Posts tagged ‘PARP inhibition’

San Francisco!

San Francisco – It’s time to switch horses for some the latest conference coverage and explore some important new findings emerging from the genitourinary world of bladder, prostate, and renal cell cancers at the ASCOGU specialist meeting held late last week.

Not that many years ago, much of this niche was dominated by numerous updates in prostate cancer, with little good cheer to write about on the other two cancers – how things have changed in such a short time!

This year there’s plenty going on in all three categories, I’m pleased to say.

Here we focus on several important trials or targets and explain why they matter and what’s significant about the findings…

Some of the agents or trials selected here are likely to receive more attention going forward as more data become available, so it behooves us to set the scene now.

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Dr Moore at ESMO18

At the recent European Society of Medical Oncology (ESMO18) Congress in Munich, arguably the data of the meeting – if the audience reaction is anything to go by – were the results from the phase 3 SOLO1 trial that were presented by Dr Kathleen Moore (right).

The results were simultaneously published in The New England Journal of Medicine in an article entitled: “Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer” (Link).

As Moore and colleagues note in the abstract:

“After a median follow-up of 41 months, the risk of disease progression or death was 70% lower with olaparib than with placebo (Kaplan–Meier estimate of the rate of freedom from disease progression and from death at 3 years, 60% vs. 27%; hazard ratio for disease progression or death, 0.30; 95% confidence interval, 0.23 to 0.41; P < 0.001).”

Dr Moore is an Associate Professor of gynecologic oncology and the Jim and Christy Everest Endowed Chair in Cancer Research at the University of Oklahoma Stephenson Cancer Center.  She kindly spoke to BSB after her presentation in the Presidential Symposium.

In addition to Dr Moore’s personal commentary on what these results mean for women with ovarian cancer, we also have some additional insights on what this data may mean for other players in the PARP space such as Tesaro and Clovis.

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Picking a PARPi – what can the biology tell us?

One of the really interesting questions I recently received from a BSB subscriber related to PARP inhibitors – they asked whether the therapies are all the same and can be considered interchangeable as a class?

Around the same time, another reader wrote in asking if there was any new information on what’s happening with PARPi combinations in breast or ovarian cancers?

This got me thinking as there has actually been some useful preclinical and clinical studies reported on both fronts that at least begin to open our eyes to new information based on research that has been reported in several places.

Thus I thought it would be useful to summarise the data and take a look at what we learned in the process.

Fair warning – some of the findings turned out to be a little bit more surprising than you might normally expect to see…

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This kind of positive news is always nice to wake up and read:

“Rucaparib maintenance therapy increases progression-free survival in BRCA mutant recurrent ovarian cancer by 77%, according to late-breaking results from the ARIEL3 trial reported today at the ESMO 2017 Congress in Madrid.”

Of course, it’s not the first PARP inhibitor to show a significant effect as maintenance therapy in ovarian cancer after initial platinum therapy and we shouldn’t assume that all drugs in the same class will have an equivalent effect until we see the data.

It is good to see confirmation of a positive impact after seeing the data from two plus lines of therapy at ESMO in Copenhagen last fall.

So what does the new readout look like, what can we learn from it, and what were thought leader reactions to the data?

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Madrid city center

Greetings from Vienna, Austria!  Fresh off a red eye… we’re en route to one European cancer conference in Germany, while writing about another one in Madrid.

This latest preview looks at some of the key IO studies that are either intriguing or have potentially interesting results that BSB readers have written in asking us about.

There are some targeted therapies thrown in too for good measure too, as there are some IO-targeted combos to look at, as well as IO-IO approaches.

What I want to accomplish in this latest preview is point out some elements of what we call ‘interestingness’ where people should be watch or wary of either jumping to conclusions or making comparisons across trials and arriving at assumptions that may not turn out to be valid. My best advice here is to always be sceptical and assume there’s no concordance and that way you won’t be caught unawares.  It’s easier said than done, though.

Indeed there were so many questions about ESMO that we needed two preview posts to cover many of the questions we received.

Part 2 should roll out tomorrow, wifi on the road permitting – stay tuned for more on ESMO17.

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The recent PARP inhibitor data has stirred up a lot of interest amongst BSB subscribers (See post: PARP! PARP! what’s hot in ovarian cancer at SGO and AACR?).

So, rather than do another AACR 2017 Preview (more coming next week!), it seemed timely to take a look at some of the interesting questions we’ve received from subscribers.

Five questions have been selected for answer in this week’s BSB reader Q&A. We don’t award prizes if your question is selected, nor do we name who asked the question, but everyone benefits when interesting questions are asked and we can all learn from each other.

As author Thomas Berger aptly said:

The art and science of asking questions is the source of all knowledge.” 

What differentiates many world class cancer researchers is frequently the scientific questions they ask in their work. The same holds true if you are a C level executive or a journalist. The quality of the answer you obtain is often dependent on the quality of the question you ask.

We hope that being better informed about the issues and topics we write about on BSB will enable subscribers to ask better questions, and in the process make better decisions.

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HI Koko Crater Flowers

Over the last week or so, we’ve received a lot of questions on the following topics relating to women’s cancers in breast and ovarian carcinomas:

  • APHINITY impact – pertuzumab and neratinib
  • PARPs in ovarian cancer – niraparib, rucaparib and olaparib
  • Seattle Genetics and Immunomedics

So this is probably a good time for a February BSB Reader Q&A post on the hot topics of the moment in cancer research.

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The huge pile of interesting scientific papers yet to be read seems to breed overnight and one constantly feels like they’re 2,000 articles behind, even with spending Friday mornings attacking them with gusto.

This was as true in my PhD days as it is now. For a scientist, these represent a lifeline and an important necessity, rather than a luxury.

In the last journal club posting we covered some hot topics in cancer immunotherapy, so this one covers a very different topic, namely targeted therapies.

It’s a good time for a new journal club post, where we tackle some of the recent published literature in oncology and highlight some important new findings that could have an impact on cancer research and development.

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We’ve had a couple of requests come in for a revival of the old conference series… ‘Gems from the poster halls’ because quite a few folks are interested in the up and coming data from small to medium biotechs.

SABCS San Antonio CrowdA bunch of my Post Doc chums in this field were at the San Antonio Breast Cancer Symposium (SABCS) meeting and gleefully highlighted mobbed posters or areas where they thought the data looked potentially interesting.

From these, we selected a few for review in today’s look at the nuggets that can be gleaned from cool and intriguing trials or preclinical research that may influence future trials.

Companies covered in this article include Seattle Genetics, Jounce, Immunomedics, Syndax and MedImmune.

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The Oncologist Journal of the Society for Translational Oncology (STO) has published a video recording on prostate cancer that is well worth watching for those with an interest in this area.

At their Sept 8, 2011 CME symposium held in Belfast, a roundtable was held entitled “Prostate Cancer: Progress & Promise.”

Moderated by Bruce A. Chabner (Mass General/Harvard), the panelists were Joe O’Sullivan (Queen’s University, Belfast), Johann De Bono (The Institute for Cancer Research) and David Waugh (Queen’s University, Belfast).

Professor de Bono in the video comments that”

“with regards to our dream of eventually treating men with prostate cancer without castrating them, which must be our ultimate goal and curing them of cancer. I think we will have to focus on for example drugs targeting ERG or ERG signaling.”

Chabner then asks the good question of whether ERG is a druggable target?

To which De Bono replies that you can drug ERG by inhibiting PARP and references a paper by the Chinnaiyan group published in the May 2011 issue of Cancer Cell.

PARP inhibition represents an interesting area of prostate cancer research.

If you would like to know more, Sally Church, PhD has written about this on Pharma Strategy Blog.  See posts on “TMPRSS2: ERG may be a more useful marker than PSA in prostate cancer” and “Personalized Therapy for Prostate Cancer – is it possible?

In the STO video, De Bono discusses why he would like to replace bone scans in prostate cancer with another imaging modality that more accurately reflects the activity of the disease. Future possibilities include use of diffusion weighted magnetic resonance imaging and novel PET tracers.

There’s also a good discussion about Alpharadin for those interested in some anecdotal commentary on experiences with it.

Another notable comment by De Bono is his belief that “taxanes work in prostate cancer primarily by targeting androgen receptor signaling.” Taxanes have typically been thought to target mitosis.

De Bono goes on to say that clinical trial data being submitted for publication shows that patients who are refractory to abiraterone, are also refractory to docetaxel when they progress on it.  The suggestion is that there may be cross resistance between abiraterone and taxanes with a subgroup of patients who just don’t do well on androgen receptor (AR) targeting drugs.  The reason for this isn’t yet clear.

A new phase 2 clinical trial is starting soon that will look at the sequencing of abiraterone and cabazitaxel.  One group will receive abiraterone followed by cabazitaxel, the other cabazitaxel followed by abiraterone.

The Belfast STO symposium was the second in a three part series. The next one will be held during ASCO GU in San Francisco next year.

Another potentially useful meeting in this area is the February 2012 AACR workshop on “Advances in Prostate Cancer Research” chaired by Arul Chinnaiyan & Charles Sawyers.

Prostate cancer remains an exciting therapeutic area to watch with tremendous progress and promise of late.

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