Biotech Strategy Blog

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

Posts tagged ‘PARP inhibition’

How – and when – should people with early stage breast cancer be treated with a PARP inhibitor?

We’re going to take a change of pace from our scientific previews from the forthcoming AACR meeting and switch to early stage cancer clinical trials readouts coming out this week.

The first one on deck is an update of the OlympiA trial exploring the PARP inhibitor olaparib as adjuvant therapy after chemotherapy in early stage germline BRCA mutation-positive (gBRCAm) high-risk breast cancer.

This is an important trial to follow given it’s the first of the PARPs to read out in early stage breast cancer in a well defined patient population with a high risk of disease recurrence.

Here, we explore the pros and cons of the latest findings and also put them in context since there’s quite a few important nuances to consider…

BSB subscribers can read our latest commentary – you can either log-in or click to access.

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Endless DDR changes and how we are going beyond PARP inhibitors

There are at seemingly endless genes associated with genomic instability and the development of cancer – there are at least 450 genes associated with DNA Damage Repair (DDR) alone, for example.

This means it is, perhaps, not at all surprising these can not only induce significant changes in various tumours, but they also might have deeper interactions between them as well, many of which we may not yet know about.

Just as we have seen some success with PARP inhibitors in patients with BRCA loss of function, so too are companies seeking to exploit additional vulnerabilities by targeting the achilles heel with other paired approaches such as ATR inhibitors in cancers where there is ATM loss of function.

There has been a raft of data in this niche from several agents in this class so it’s time to turn our attention to reviewing what we learned from the many subtleties and nuances that inevitably abound in this DDR subniche, including recent data presented by Repare Therapeutics at the AACR-NCI-EORTC meeting…

BSB subscribers can read up on our latest commentary and analysis from the cancer conference season for our ongoing TRIPLE meeting coverage – you can either log-in or click to access our latest analysis.

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Coming back full circle

Where are we headed in the DDR niche?

The dog days of summer always seem to portend a mix of sunny days and stormy skies ahead…

In this latest report we cover important issues around homologous repair deficiency (HRD), new replication stress targets, as well as how both analysis and assays are being developed to meet the evolving needs of the field.

There is much nuance going on behind the scenes, which will be important to keep up to date with, including some tumour types not previously associated with DNA damage repair, something we highlight in this post.

These findings might have implications for future regimens and may explain some of the undetected mechanisms of resistance we are seeing in existing trials being presented at ESMO or the forthcoming Molecular Targets (TRIPLE) meeting.

There are also diagnostic developments to think about, not just therapeutic ones…

BSB subscribers can read more on our latest update regarding HRD and DDR inhibitors, plus our latest expert interview from ASCO – you can log-in or click to access the new content.

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Is olaparib scaling new heights in OlympiA?

Source: Wikipedia

We first wrote about the fascinating and complex space way of synthetic lethality and PARP inhibition way back in 2006 when the early preclinical developments and targets were just emerging and finally here we are – 15 years later – with the very first phase 3 data in the adjuvant setting.

It’s not often I get to highlight someone and their extensive research from my alma mater, but it’s a delightful opportunity to put it on the front page for a change. The gritty urban setting is a far cry from the romance of the other Kings College (in Cambridge), although the two cities do overlap somewhat in this particular story.

What can we learn from the latest clinical development in early stage breast cancer and what don’t we yet know?

There’s actually quite a lot to ponder and digest here…

BSB subscribers can read more on our initial perspectives regarding PARP inhibition in early stage breast cancer and the OlympiA trial, subscribers can log-in or you can click to read our ASCO21 coverage.

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A phoenix rises from the ashes

A phoenix rises from the ashesResilience in purpose and openess in strategic direction are key dual features in the DNA of strong biotechs which succeed in the long run and live to survive the roller coaster ride that is oncology R&D.

Setbacks are to be expected, but what matters more is not that they happen, but the mettle and toughness to deal with them over time.

There is no doubt Clovis Oncology encountered a major setback with the abandonment of rociletinib in lung cancer, while the rise of PARP inhibitors meant they were well placed with the rucaparib development.

Beyond these events, what next?

It’s time to take a bigger picture look at what’s happening with the pipeline and where they might be heading since there could be some surprises in store…

To learn more from our oncology analysis and get a heads up on the latest insights and commentary pertaining to ESMO20 virtual congress, subscribers can log-in or you can click to gain access to BSB Premium Content.

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ESMO20 Preview 4 – Targeted therapies to watch out for

Not in Madrid – with the global pandemic continuing to exert a significant effect on the cancer conference season, the annual meetings continue apace virtually.

Plaza de Cibeles, Madrid

For this year’s ESMO meeting we have already covered immunotherapies, both early and late stage pipeline highlights and now it’s time to explore what to watch out for over the weekend on the early to mid stage targeted therapy front.

The good news is there is some potentially practice changing data being presented, as well as some novel approaches in preclinical development emerging. These should be hitting the clinic in the near to medium term future.  On the other extreme is the more common problem whereby a few agents are showing signs of not holding up to their early promise/hype.

Let’s now take a look at what we can learn in the fourth and final ESMO Preview for 2020…

To learn more from our oncology analysis and get a heads up on insights and commentary pertaining to ESMO 2020, subscribers can log-in or you can click to gain access to BSB Premium Content.

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New developments in Genitourinary cancers

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.

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

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Why are the SOLO1 data so compelling?

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.

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Picking PARP inhibitors apart

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…

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

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The changing face of ovarian cancer

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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