Biotech Strategy Blog

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

Posts tagged ‘olaparib’

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.

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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…

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Going beyond PARP monotherapies

It amuses me to realise that I’ve been writing about and following PARP inhibition since 2006 or so, when the field was in that twilight zone of early drug development between preclinical and clinical, thus just beginning to hit some sort of consciousness and broader interest in cancer research.

The AACR Molecular Targets meeting in 2009 was the first scientific meeting I covered as a science writer on the old Pharma Strategy Blog, which focused on early drug development from preclinical to phase 2 – after that I would rapidly lose interest and move on to the next new shiny scientific lure to research and discuss. No doubt this eager new writer ran about like an overenthusiastic little puppy in the poster halls chatting to scientists about their research, much to the amusement of the more staid press room, who at that time probably never ventured out of the darkened basement gloom.

In one of the press briefings there, I met an engaging and thoughtful scientist who was presenting his poster on PARP and synthetic lethality. He kindly took the time to explain in plain English a commonsense analogy that was most helpful for grasping complex concepts. Having sat through several long talks from luminaries in the field such as Drs Hillary Calvert and Alan Ashworth that covered double strand breaks and DNA repair mechanisms, it was a most welcome respite in the hurly burly of the conference!

Imagine his imagery…

You have a four legged coffee table or wooden chair and one of the legs breaks off or is damaged. The table remains standing, albeit less stable than before. Now a second leg breaks, and inevitably, the table is so unstable that it falls over.

Once you grasp that simple analogy for synthetic lethality, you have the basic idea of DNA double strand breaks and how inefficient repair can lead to vulnerabilities in the tumour that can be exploited.

The scientist I spoke to in Boston back in 2009 was Dr Mark O’Connor.

He was involved in DNA damage response research at a little known private company in Cambridge, UK called KuDos, who were subsequently acquired by AstraZeneca. Nearly a decade on and Dr O’Connor is still at the company; he now heads up their DNA damage response area.

Dr Mark O’Connor, AZN

With olaparib (Lynparza) since approved by the FDA in ovarian cancer and slated for the ASCO 2017 plenary session for HER2- breast cancer, things have certainly changed a lot since those early heady days of KuDos and the R&D journey has not been without its notable ups and downs along the way.

In Chicago earlier this month, I had the pleasure of catching up again with Dr O’Connor to learn more about the journey, and importantly, where things are going next.  It’s quite an interesting roller coaster ride, to be sure!

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An in-depth look at OLYMPIAD in HER2 negative breast cancer

Often times when we see promising data presented at a cancer conference, we interview a thought leader and post the expert opinion with additional commentary and insights.

ASCO17 OlympiAD Plenary

At ASCO, we decided to take a different approach, a twist on the usual fare… given that two of the phase 3 trials, OLYMPIAD and APHINITY, received significant attention and focus involved breast cancer, we reached out to numerous experts and curated their sentiments on both studies.  For completeness and fair balance, these included industry and academic opinions.

Today, we begin with the OLYMPIAD trial presented by Dr Mark Robson on behalf of his colleagues exploring the role of the PARP inhibitor, olaparib (Lynparza), in HER2-negative metastatic breast cancer with germline BRCA mutations.

There’s a lot to consider here, not least is where do we go next from here and which PARP combination approaches are researchers most excited about?

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Going Beyond PARP in DNA Damage Repair

We now turn our sights to targeted therapies and DNA Damage Repair (DDR). This is an important topic that has seen much focus in ovarian cancer of late and will likely see renewed interest in breast cancer at the forthcoming ASCO meeting next month. As we segue from one set of conference coverage to the next, there is inevitably going to be overlap, which is a good thing here as it helps with background and preparation in getting up to speed.

There is no doubt that DDR has had a bit of chequered history over the last decade, whether it be the spectacular (and sadly predictable) flop of Sanofi’s iniparib in triple negative breast cancer (TNBC), the negative ODAC incurred by AstraZeneca’s olaparib in ovarian cancer, or AbbVie’s more recent veliparib failures, to the much more positive events such as three PARP drugs now approved in different lines of therapy in ovarian cancer (olaparib, rucaparib and niraparib).

If ever there was a niche for the roller coaster ride that is oncology R&D, it has to be PARP inhibitors.  There’s much more to DDR than just PARP though.

Indeed, there are multiple intriguing targets to explore and also the potential for combinations with cancer immunotherapy approaches that may yield encouraging results in the future.

Can we go beyond ovarian cancer into other tumour types and if so, which ones look encouraging and how woluld we go about exploring those idesa? What makes one approach more successful than another?

Here we explore the world of DDR through the lens one company’s approach and look at what they’ve done, where are they now and where they hope to be. It certainly makes for an intriguing and candid fireside chat.

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How do we get cancer immunotherapy to work in Prostate Cancer?

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).

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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FDA Approval of Niraparib is a Failure for Precision Medicine

Following the recent approval of Clovis’s rucaparib (Rubraca) by FDA under priority review as monotherapy for the treatment of women with certain types of advanced ovarian cancer, then impressive SOLO-2 maintenance data after initial chemotherapy at SGO earlier this month, PARP inhibitors continue to be in the news.

There’s always more though!

This afternoon saw the approval of Tesaro’s PARP inhibitor niraparib (Zejula) by the US Food and Drug Administration (FDA) for maintenance treatment of women with ovarian cancer who are in a complete or partial response to platinum-based chemotherapy (Link to label).

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Asking Good Questions is both an Art and a Science

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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AACR 2017 Preview 5

There’s no secret or surprise with our latest AACR Preview as this week the focus takes a slight turns or detour to the annual meeting of the Society for Gynecology Oncology being held in National Harbor, Maryland.

PARP inhibitors in ovarian cancer have been a hot topic since last autumn when the PARP inhibitor data dropped at ESMO in Copenhagen, and was not without controversy either.

We’ve been following the trials, tribulations and even machinations, of the clinical development of olaparib, rucaparib and niraparib for a while now so what’s in store in the latest round of salvoes?

And importantly, what else can we expect to see in DC at AACR next month?

For a tumour type that hasn’t received much attention over the last decade or two, things are distinctly picking up.  Is it all good though?

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On APHINITY, SOLO2 and Immunomedics

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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