Biotech Strategy Blog

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

Posts tagged ‘San Antonio Breast Cancer Symposium’

Whew, having just finished the American Society of Hematology (ASH) meeting, we run on to the breast cancer symposium in San Antonio (SABCS), making for a very busy week of data deluge!  Our Post ASH analysis will also run concurrently for a few days.

There are also a number of interesting areas to look out for in terms of interesting breast cancer developments.

Premium subscribers can find out more about the following below:

Companies: Roche, GSK, AbbVie, AstraZeneca, Novartis, Lilly

Drugs: Herceptin, Avastin, Perjeta, Tykerb, veliparib, olaparib, BKM120, ramucirumab, PD-1, PD-L1

Here’s a quick preview of some of the landmark data emerging from this conference, some positive, some negative.

The forthcoming annual meeting of the American Association for Cancer Research (AACR) in Washington DC is a must attend for anyone interested in cancer research and new cancer drugs in development.

AACR 2013 Annual Meeting Banner Screenshot

Many readers will know that one of the hallmarks of cancer is the evasion of apoptosis or cell death.  Drugs in development that act as an inhibitor of apoptosis proteins (IAP) are starting to show promise against this target.

Novartis IAP Inhibitor LCL161

At the 2012 San Antonio Breast Cancer Symposium (SABCS), a phase 1 trial with LCL161, a novel-IAP antagonist from Novartis, showed promising responses in triple negative breast cancer when given in combination with paclitaxel chemotherapy. The SABCS data showed that in the 52 patients treated with LCL161, a complete response was observed in 1 patient, and a partial response was seen in 15 patients.

Caution must obviously be expressed at extrapolating from early-stage data in a non-randomized trial.

Several other companies have IAP antagonists in early development, including Curis (CUDC-427).

  • Curis announced in November they had licensed GDC-0917 from Genentech. I am hopeful there will be new data on CUDC-427 at the AACR annual meeting.  At the recent Citi Global Healthcare Conference on Feb 25, 2013, Curis stated they could start phase 2 development of CUDC-427 by mid-2013 and were looking at it in combination with capecitabine (Xeloda) in breast cancer as well as monotherapy.
  • Ascenta Therapeutics licensed their IAP inhibitor AT-406 to Debiopharm in August 2011.

Nature Reviews Drug Discovery has a review article on “Targeting IAP proteins for therapeutic intervention in cancer” for those interested in learning more about some of the compounds in preclinical and clinical development, and the scientific rationale behind this target.

IAP inhibitors are an interesting class of compounds to watch as they move forward in clinical development.

IAP Inhibitors may promote Bone Metastasis

Research published in the February 2013 issue of the AACR journal Cancer Discovery shows that in mouse experiments a side-effect of IAP inhibitors is promotion of osteoclast activity.  Whether these preclinical results in animal models translate to man remains to be seen, but the research by Chang Yang and colleagues from the Washington University School of Medicine in St Louis, MO is worth noting.

Cancer Discovery Research Article Chang Yang

In simple terms, osteoclasts are the cells that remove bone as part of a dynamic equilibrium with osteoblasts, the cells that produce and lay down new bone.

An increase in osteoclasts caused by IAP antagonists activating alternative NF-κB signalling through NF-κB-inducing kinase (NIK) results in the disruption of normal bone metabolism.  In mouse experiments, this led to over-degradation of bone and osteoporosis (pathological bone loss), as well as providing a microenvironment that favors tumor expansion and metastasis.

Osteoclasts embedded in the bone matrix also release tumor growth factors, so if there are more osteoclasts then more growth factors are produced resulting in the creation of a more favourable microenvironment for bone metastasis.

In addition to showing the effects of IAP antagonists on the bone microenvironment, Chang Yang and colleagues demonstrated that drugs that prevent bone resorption such as zoledronic acid were able to decrease the incidence and severity of bone metastasis.

Many breast, cancer, prostate and lung cancer patients end up with bone metastases, which is why bone targeted agents have an important role to play in the treatment of the disease.

They conclude in their Cancer Discovery research paper that “future clinical trials of IAP antagonist-based therapy may require detailed examination of this potential for enhanced bone metastasis and osteoporosis, as well as possible combination with antiresorptive agents.”  

The potential implications of this research is that bisphosphonates such as zoledronic acid and RANKL-targeted compounds, such as denosumab, may need to be used in conjunction with IAP antagonist treatment.

This is an important finding. If the animal results translate to humans, then concomitant administration of a bone target agent may be necessary.  Future clinical trials of IAP antagonists could end up with more complex and expensive study designs if bone side effects needs to be monitored and addressed.

I look forward to learning more about IAP antagonists at the AACR meeting in April, and to following progress in this novel class of new drugs that seek to address one of the hallmarks of cancer.

ResearchBlogging.orgYang, C., Davis, J., Zeng, R., Vora, P., Su, X., Collins, L., Vangveravong, S., Mach, R., Piwnica-Worms, D., Weilbaecher, K., Faccio, R., & Veis Novack, D. (2012). Antagonism of Inhibitor of Apoptosis Proteins Increases Bone Metastasis via Unexpected Osteoclast Activation Cancer Discovery, 3 (2), 212-223 DOI: 10.1158/2159-8290.CD-12-0271


The San Antonio Breast Cancer Symposium (#SABCS) starts next week (Dec 4 – 8).

Dr Jose Baselga Interviewed at 2011 San Antonio Breast Cancer Symposium Last year at SABCS, Dr Jose Baselga presented the results of the CLEOPATRA phase III trial in HER2+ metastatic breast cancer.

An impressive 6.1 months increase in progression free survival (PFS) of 18.5 vs. 12.4 months was seen by the addition of pertuzumab (Perjeta) to the combination of trastuzumab (Herceptin) and chemotherapy (docetaxel). You can read more on Pharma Strategy Blog.

Earlier this year, following pertuzumab’s approval by the FDA, Roche/Genentech announced that the CLEOPATRA study results demonstrated that women taking the pertuzumab, trastuzumab and chemotherapy combination lived significantly longer, i.e. an overall survival (OS) benefit. The exact amount of the OS benefit is not yet known, but the data will be presented next week in San Antonio. This is exciting news!

I will not be at SABCS due to the overlap with ASH, but like many will be following via Twitter. Without wishing to offend anyone not included, here’s my starting list of people I will be following for news and commentary:




  • Roche at Congresses @congressconnect (update Dec 6: surprising – tweeted that not covering SABCS this year)
  • Boehringer @Boehringer (added Dec 3)

Patient Advocates/Advocacy & Support Groups


I am sure there will be a lot of people contributing to the conversation from San Antonio so do follow the #SABCS Twitter hashtag for additional people you may wish to follow.

In case you missed it, here is the Pharma Strategy Blog video from SABCS 2011, presented by Sally Church, PhD (@MaverickNY):


I have had the privilege to attend many scientific and medical congresses this past year, and my belief from listening to many presentations is that drug development innovation comes from understanding basic biology, then applying this knowledge.

Lisa Coussens (UCSF) at the 2011 San Antonio Breast Cancer Symposium (SABCS) provided a good example of how scientific knowledge is being translated into medicine and applied to drug development.

In her plenary presentation, she outlined how our understanding of the biology of macrophages and the importance they play in breast cancer may lead to new drug targets.  As an example of this, she showed pre-clinical animal work on the Plexxikon drug PLX3397.  A human phase 1b/II clinical trial will start in the near future.

I have aggregated some of the live tweets from the session using Storify.  Social media can be a powerful tool to share highlights and top-line messages with those not at meetings, as well as have a real-time conversation with those in the same session. It was disappointing that the lack of wifi in meeting rooms prevented many international scientists and researchers from sharing their insights.

I look forward to watching the development of PLX3397, and am sure that we will see more drug development targeting macrophages.  Coussens presentation was outstanding and the highlight of SABCS for me.

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San Antonio – there is a lot of exciting new data at the San Antonio Breast Cancer Symposium (SABCS) this week.

As Sally Church pointed out in her SABCS video on Pharma Strategy Blog, the update to the BOLERO2 data  (previously presented by Jose Baselga at ECCO/ESMO 2011 in September) will be presented later this morning at SABCS.

As a side note it is worth noting that the NEJM paper published yesterday contains the Stockholm data, not the updated data that will be presented later today that will show further improvement in progression free survival (as compared to placebo) in post menopausal ER+ HER2- women who took everolimus combined with exemestane.

Despite the presentation of exciting data at SABCS this week, my opinion is that this is a good meeting, but not a great one (yet). The reason is not the quality of the science being presented this week, but the lack of quality discussants.

The unheralded discussant is the expert that puts the science in context for the audience. Whether it’s a discussion of a simple poster or of a plenary session, the discussants play an important role.

Yesterday at SABCS I sat through two general sessions (the equivalent of plenary sessions at other meetings) in the cavern like auditorium that I estimate sits two thousand attendees.

Of the 15 presentations, only the 3 on bisphosphonates were given a discussant. That is why this meeting to me is good, but not great.  Both ASCO and ESMO/ECCO do a much better job at having a expert put the data in context in an independent and unbiased review.

Why is a discussant important when it’s all about the scientific data?

The challenge with medicine, law and any other professions is that there is so much new data that we can only be experts in a very small area or subset of knowledge.

At SABCS there are basic scientists, medical students, researchers, oncologists, community physicians, patient advocates and survivors. What does the data presented mean to them?

The discussant looks at many aspects of a presentation and can be critical, positive and negative in their observations about:

  • Clinical Trial Design:  what were the limitations?
  • Results:  did it meet the endpoints, was the data significant?
  • Adverse events: is the AE profile a concern?
  • Comparison to literature:  how does this data compare to the literature?
  • Future research:  does this data suggest rational future trials or research?
  • Practice implications:  does the data impact the standard of care?

There are many more questions that come to mind.  Listening to a good discussant brings science to life.

It is, however, challenging being a discussant because like writing a blog, you are generating original content and expressing an opinion.

My view is that if a presentation is good enough to receive an oral presentation at a major meeting, then it’s good enough to be discussed.  I hope that SABCS will offer more discussants in future years and make this a great scientific meeting in return.

San Antonio – at the San Antonio Breast Cancer Symposium (SABCS), the Institute of Medicine (IOM) report on “Breast Cancer and the Environment” was eagerly anticipated.

Published today, the report appears to me to offer little in the way of new insight into how women should live in order to lower their environmental risk of breast cancer.

The review of the scientific literature undertaken by the IOM notes that epidemiologic studies have shown an association between some environmental risk factors and breast cancer. These include ionizing radiation & combination hormone therapy.

The report goes on to say that for many other environmental factors, the evidence is “limited, contradictory or absent”.

The conclusion from the report is that “women may have some opportunities to reduce their risk of breast cancer through personal actions:

  • Avoiding unnecessary medical radiation throughout life
  • Avoiding some forms of postmenopausal hormone therapy
  • Avoiding Smoking
  • Limiting Alcohol Consumption
  • Increasing physical activity
  • Minimizing weight gain (for those at risk of postmenopausal breast cancer)

Much of the above advice would apply to anyone looking to maintain a healthy lifestyle, but it’s hard to quantify the potential benefit.  The report notes the “potential risk reductions for any individual woman will vary and be modest.”

Given that non-smokers can end up with lung cancer, it’s hard to predict who will get cancer and to what extent exposure to environmental factors may have an impact.

Are some people more disposed to environmental risk factors than others?

As we move towards personalized medicine and a greater understanding of the individual genome, it will be interesting to see if we will gain more insight into who is most at risk from the environment.

Perhaps in the future we will be better able to identify those individuals whose genetic make-up result in them being more at risk from others of certain environmental stresses.

In the meantime, if you have an interest in the IOM Breast Cancer and the Environment report it is freely available to download.

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