Biotech Strategy Blog

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

Posts tagged ‘everolimus’

What would Charles Darwin make of renal cell carcinoma?

At the last count, the renal cell carcinoma (RCC) space is quite competitive with five VEGF inhibitors (sunitinib, sorafenib, axitinib, pazopanib and bevacizumab), two mTOR blockers (temsirolimus and everolimus) and not forgetting IL–2, all approved by the FDA for the treatment of advanced disease.

Much of the recent focus has been on sequencing, exploring combinations (generally too toxic with little added benefit), and evaluating the potential for novel immunotherapies in development such as checkpoint inhibitors. Biomarkers are few and far between, making it hard to rationally decide which therapy each patient should get and in which sequence.

The key question is, why is this tumour type so challenging from a clinical and scientific perspective?

Screenshot 2015-03-23 12.44.32Recently, new data has begun to emerge that may help inform or enable us to switch to new approaches.  While the urologists are eagerly watching the live surgery on the EAU cam, we highlight research data presented at the European Association of Urology (EAU) in Madrid and take a look at how the underlying biology of RCC can elevate our knowledge about where the potential future strategies and blueprint might lie, if we want to facilitate exciting new developments in this field.

To learn more about our latest insights, subscribers can log-in or you can purchase access to BSB Premium Content. 

This content is restricted to subscribers

ESMO 2014 Poster Preview

Yesterday, the European Society of Medical Oncology (ESMO) released the abstracts to the poster and poster discussion sessions.  This preview will be quite long by nature of it being the first time we get a look at the topline details behind some of the key sessions and their abstracts for both immunotherapies (especially checkpoint inhibitors) and targeted therapies.  This includes posters and their discussion sessions, plus poster late breaking poster titles.

For reference, you can find the ESMO 2014 poster and poster discussion abstracts can be found here.

In addition, there appears to be some pretty cool presentations in the Special Symposia, which are rather like ASCO scientific symposia and contain a lot of useful information and often strategic ideas about where thought leaders see hot topics going in the future.  This can be very helpful in learning about possibilities for new clinical trials ahead of time. As we focus on the poster highlights today, do check back tomorrow for a detailed look at the scientific symposia.

Premium subscribers and those interested in signing up for our Conference Coverage service can log-in to access our latest insights from the ESMO 2014 meeting.

This content is restricted to subscribers

Novel targets and approaches in triple negative breast cancer

“You may say I’m a dreamer

But I’m not the only one.”

John Lennon, Imagine

As part of our ongoing series on the AACR Previews, today I want to take a closer look at some interesting scientific and clinical data in triple negative breast cancer (TNBC).  One reason for this is that we need to remember that the disease, as currently defined, is essentially what’s left after taking out the ER+, HER2+ and inflammatory breast cancer subsets. In other words, it’s a very heterogeneous catch-all population, making clinical trials rather challenging at best. It also means that the chances of success in general all-comer trials is rather low.

It is my hope that as we learn more about the biology of this disease, we may see further subsets be defined by molecular peculiarities, much in the same way that gastrointestinal stromal tumours (GIST) were defined by KIT expression and CD117. Once we have more homogenous subsets, it will be easier to conduct trials just looking at those specific patients, thereby improving the chances of clinical success with therapeutic intervention.

There’s been a lot of work focused on this area over the last few years, so it seems a good point to find out where the progress has got to.

Without much further ado, what can we learn about the biology of TNBC from AACR this year and which potential new targets might emerge?

To learn more insights on this intriguing topic, subscribers can log-in or you can purchase access to BSB Premium Content. 

This content is restricted to subscribers

What can we learn from exceptional responders in cancer trials?

Following on from yesterday’s post on the potential for small basket trials in ER+ breast cancer with the ESR1 mutation, I wanted to highlight another area where these type of highly focused and rational studies appear to be not only useful but also potentially produce stunning responses.

Some of you will recall the fascinating and widely told story of a single bladder cancer patient at Memorial Sloan Kettering who was resistant to multiple lines of therapies. The team sequenced the genome and found a rare TSC1 mutation. Importantly, this is known from pediatric astrocytoma studies, to be sensitive to an mTOR inhibitor, everolimus (Afinitor). The refractory patient was given the drug and responded well. The rest is history, as they say.

Can we learn more from these type of appraches, i.e. genomic sequencing of patients who have relapsed after initial therapy?

Can we also learn more from the few exceptional responders in clinical trials – what was unique about their response that elicited such a stunning effect?

The short answer is a resounding yes.

Subscribers can log-in to read our latest insights or you can purchase access to BSB Premium Content. 

This content is restricted to subscribers

ECCO 2013 Notes from the Road – Day 1

It’s been a long 14+ hours here on the first day of ECCO in Amsterdam and I’m starting to flag a little. The fun part of being in Amsterdam is renting an apartment, living like a local and cycling to/from the conference centre on rickety Dutch bicycles!

That said, having been aghast at the poor wifi and frustrated with nearly not being allowed in a key session over badge confusion, plus scheduling of multiple key sessions at once, we decided to make the best of it and be selective. This morning, for example, I ran from lung to melanoma to breast to the  poster hall and back again to a lung session. Pieter had the luxury of enjoying the prostate cancer session in comparison!  By 6pm the BMS corporate symposia on immunotherapy was out – the brain was dazed and jetlagged, the car needed fuel (preferably of the rocket variety) and also a glass of wine!

We will post some more detailed notes later, but today I wanted to offer some top line thoughts on some of the highlights:

To learn more insights on this intriguing topic, subscribers can log-in or you can purchase access to BSB Premium Content. 

This content is restricted to subscribers

Of Mice and Men

One of the themes of this blog is innovation in biopharmaceutical new product development. Innovation can take many forms ranging from nanotechnology based drug delivery to a novel scientific mechanism of action.  The March 17, 2011 edition of Nature, highlights how innovative preclinical animal models are having an impact on drug development.

In their article on translational medicine, “Cancer lessons from mice to humans”, David Tuveson and Douglas Hanahan, describe how preclinical mouse models helped predict the recent phase III clinical trial results for sunitinib and everolimus in pancreatic neuorendocrine tumor (PNET).

The data was a major breakthrough for this disease. As Sally Church noted on Pharma Strategy Blog, sunitinib doubled the progression free survival (PFS) time and improved OS.

Tuveson and Hanahan in Nature note that “a vast number of potential anticancer drugs are currently in the pipelines of biopharmaceutical companies.” The challenge is not one of a shortage of candidates nor of potential targets, but in deciding which have most promise and where to spend valuable clinical development resources.

The authors conclude that there’s now optimism that genetically engineered mouse models may be able to mimic the progression of human cancer at the cellular and tissue levels. The mouse model of PNET (RIP-Tag2) successfully predicted that sunitinib and everolimus would be effective in treating humans.

Of course, not all human cancers can be modeled and adaptive resistance can subsequently occur in clinical trials, suggesting that preclinical models do have their limitations.

I hope we will see further innovation in mouse models of human cancer as translational medicine develops.

ResearchBlogging.orgTuveson, D., & Hanahan, D. (2011). Translational medicine: Cancer lessons from mice to humans Nature, 471 (7338), 316-317 DOI: 10.1038/471316a

error: Content is protected !!