Biotech Strategy Blog

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

Posts tagged ‘olaparib’

Recently, PARP inhibitors have been back in the news for several reasons, including the publication of the olaparib (AstraZenca/Merck) advanced mCRPC data in the New England Journal of Medicine from the phase 3 PROfound trial and the announcement regarding achievement of the key secondary endpoint of overall survival. As Dr José Baselga quite rightly noted, this is very good news indeed because:

“Overall survival in metastatic castration-resistant prostate cancer has remained extremely challenging to achieve.”

We’ve rather more trial misses in this disease setting than successes from various therapies over the last few years including ipilimumab, PROSTVAC, alisertib, and atezolizumab, to name a few off the top of my head.

Related to mCRPC, let’s also not forget the upcoming PDUFA date later this month for Clovis’s rucaparib in the very same indication.

Not to be outdone on the PARP front, just a few days GSK received FDA approval for niraparib as first-line monotherapy maintenance therapy for women with platinum-responsive advanced ovarian cancer – regardless of biomarker status – based on the phase 3 PRIMA study presented at ESMO last year and simultaneously published in the NEJM. Recall that the majority of women (51%) had homologous-recombination deficiency (HRD) and this subset saw the greatest benefit.

Flying high in the DDR space?

We have now seen clinical benefit in the PARP inhibitors in four tumour types driven by DNA damage repair (DDR) deficiencies, namely ovarian, breast, pancreatic, and prostate cancers.

How do we go about extending the concept of DDR in terms of the biology of other tumour types?

A number of related pathway targets have been investigated, including ATM/ATR, Chk1, Wee–1 and others, with mixed success.

It’s not the nature of oncology R&D to stand still, however; what if we could turn things on their head and think creatively about the problems still to be addressed?

One particular new company to the PARP space is doing just that… so what are they doing and what’s different about their approach?

To learn more from our oncology analysis and get a heads up on new insights and commentary subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

Who’s King of the PARP castle?

After yesterday’s review and expert commentary on the phase 3 PROfound trial presented in the Presidential Session at ESMO 2019, we’re continuing our look at PARP inhibitors in advanced prostate cancer.

Perhaps surprisingly, there were a lot of insights to be found in the posters that were presented and discussed at the meeting for other PARPs in clinical development.

How do these stack up against olaparib? We’re not fans of cross-trial comparisons as they always come with a mandatory health warning, but if you want to consider the emerging landscape, it is important to be aware of the different patient populations, lines of therapy, and details of the trial designs.

For additional perspective at ESMO19, we spoke to a European prostate cancer expert who kindly talked about his clinical practice and also offered insights into a PARP clinical trial he and colleagues presented in Barcelona.

Who will be King of the PARP castle in advanced prostate cancer?

To learn more from our latest oncology conference insights and get a heads up on our latest post ESMO Coverage and reflections, including a specialist thought leader interview, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

We’ve heard much about the role of PARP inhibitors in ovarian and breast cancers where there is sensitivity to these agents in women with DNA damage repair defects, but what about advanced prostate cancer?

Following the publication of the phase 2 trial TOPARP in the NEJM in 2015, we’ve been eagerly awaiting the outcome of a series of phase 3 studies with these agents in metastatic prostate cancer in multiple different lines of therapy.

Dr Oliver Sartor at ESMO19

Following on from our daily coverage from ESMO in Barcelona last week where we looked at some of the pros and cons as they appeared during the presentation by Dr Maha Hussain (Chicago) from the PROfound trial, it’s time to share some expert opinions.

The study she presented evaluated the PARP inhibitor, olaparib, versus next generation AR anatgonists abiraterone or enzalutamide in refractory metastatic castrate-resistant prostate cancer (mCRPC).  Interestingly, it soon became rapidly clear that many casual observers missed some important nuances from the myriad of top-line news articles and summaries.

The devil, as always, is in the details.

To further our readers education on this important topic, BSB interviewed a prostate cancer thought leader, Dr Oliver Sartor (right) for his personal perspectives and look at the take homes from the lens of an experienced triallist in this niche.

Let’s see what he had to say about PARP inhibitors in advanced prostate cancer, as well as the PROfound and TRITON studies…

To learn more from our latest oncology conference insights and get a heads up on our latest ESMO Coverage, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

We’ve been writing about PARP inhibitors since 2006!  Who knew this target would have multiple legs over a dozen years on?

Barcelona

In this post we’re taking a look at some of the noteworthy presentations at ESMO19 around targeting DNA damage repair (DDR) and how they act through synthetic lethality and/or the generation of immune response to kill cancer cells in GU cancers.

It’s a fascinating area where we are seeing convergence between immunotherapy and genomic instability, one of the hallmarks of cancer.

The abstracts for ESMO19 are not yet available, so in this post we’re only providing context and setting the scene for some of the presentations we are looking forward to, as well as raising some key questions that we hope will be answered in Barcelona.

To learn more from our latest oncology conference insights and get a heads up on our latest ESMO Preview, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

It’s the dog days of summer and yet there’s a lot happening on the DDR front from multiple angles.

After a short break from science, this makes now a really good time to reflect and take stock in order to explore some of the key issues facing the field, especially in terms of future combination approaches.

Research that’s appearing now may influence future trial designs – always a nagging worry in Pharmaland that the standard of care can change before you even get your own phase 3 readout! No one likes to be pipped to the post, after all.

With the early WEE–1 news this week and a raft of new PARP readouts, there is much to discuss and also plenty of nuance and subtlety to consider carefully because what looks obvious at first blush may not actually be the case based on prior evidence that many will have forgotten about.

So grab a cup of iced coffee and shades and settle down under your sunbrellas for a pleasant and easy to read review of the various trials, settings, combinations and DDR pathway considerations…

To learn more and get a heads up on our latest oncology insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

Chinatown Chicago

One of the things we try to do on BSB is tread paths that aren’t well travelled.

It’s a bit like coming to Chicago and visiting areas such as Chinatown that are beyond the common tourist sights. It can take a bit of effort, but often delivers a memorable experience in the process.

In this final preview of #ASCO19 before the educational sessions start tomorrow, we’re offering up 10 abstracts that we think are underrated and noteworthy of closer attention.

Like any guide book our recommendations are subjective, but if you’d like to read more then subscribers can login or you can purchase access.

To learn more from our latest conference coverage and oncology insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

DNA Damage Repair (DDR) has come a long way over the last decade or so from preclinical development through clinical trials, including some notable failures along the way. What began initially with PARP inhibitors, has now expanded into other related targets in the pathway, including ATM/ATR, WEE–1, Chk1/2, DNA-PK, and even Fanconi anemia genes such as FANCA/BC/D1, BRIP1 and PALB2, which are considered an indication of BRCAness where there is also chromosomal instability and homologous recombination.

Top 10 DDR targets and molecules at AACR19

At AACR last week, there was plenty to learn about in the ever-expanding DDR niche in terms of new data from a relatively new target such as DNA-PK to updated clinical data on WEE–1 and Chk1 inhibition to early data on PARP in a new tumour type to add to the growing list of ovarian, breast, and prostate cancers that are impacted by DDR therapies.

Included in this post are 10 key targets or molecules in the DDR niche that are of potential interest to readers – we explain why we included them and why the data matters.

Here we take a look at the highlights that we came across in this mini review, which should be useful preparation ahead of yet more clinical data likely being presented at ASCO and ESMO later this year.

To learn more and get a heads up on our latest oncology insights and coverage, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

The annual ASCO-SITC meeting (#ImmunoOnc19) was held in San Francisco this year and has come a long way from the inaugural event we attended in Orlando.

Finding the signals amongst the noise

In the original 2017 event, I vividly recall as stirring presentation from Dr Limo Chen on targeting CD38 in solid tumours, last year we wrote an update on GU cancers including the STING pathway.

What’s in store from San Francisco and how do we go about finding key signals from the noise?

Over the next two posts I’m going to focus on new findings in various approaches that either look interesting and worth watching, or where there are lessons that can be learned for future developments.

This time around, some of the highlights surprised even me…

To learn more from our latest conference coverage and oncology insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

At one point not too distant in the past, all the big news seemed to flow out of advanced prostate cancer with abiraterone and enzalutamide vying for attention, followed by occasional news on ARN–509, ODM–201, galeterone (remember that one from Tokai with all the AR-V7 kerfuffle?), radium Ra–223 dichloride, cabazitaxel, denosumab, ipilumumab, PROSTVAC, brachyury, and a few others. Predictably, not all were successful, and the count is still out on some.

San Francisco

In our latest conference coverage, we take a look at what we can learn from riding the prostate cancer train at ASCO GU ahead of the presentations in San Francisco tomorrow.

We will be updating this review as more data become available with the presentations, so do grab a cup of joe and settle down for some interesting reading ahead of time… this should get you all up to speed on the journey there!

To learn more from our latest conference and oncology insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

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.

To learn more from our latest assessment and get a heads up on our oncology insights, subscribers can log-in or you can click to gain access to BSB Premium Content.

This content is restricted to subscribers

Free Email Updates
Subscribe to new post alerts, offers, and additional content!
We respect your privacy and do not sell emails. Unsubscribe at any time.
error: Content is protected !!