Transforming Treatment Together for HER2 Targetable Cancers
As a result of the coronavirus SARS-CoV-2 pandemic, the American Society of Clinical Oncology (ASCO) is holding its annual meeting virtually for the first time in its history. This is just one example of how the scientific community is rising to the occasion to ensure the continuous exchange of groundbreaking research and maintaining momentum to advance science for patients with cancer. Now more than ever, we must find new and innovative ways to collaborate on science’s biggest challenges. In advance of ASCO20, Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology R&D, Daiichi Sankyo and José Baselga, MD, PhD, Executive Vice President, R&D Oncology, AstraZeneca connected to discuss the power of collaboration in oncology R&D.
Q: Why is collaboration so critical in oncology?
Our goal as researchers is to push the boundaries of science to deliver life-changing medicines for patients with cancer, and collaboration has always been critical to achieving this goal.
With increased cancer genetic profiling, we have learned more about the different biomarkers that drive disease in individual patients. These insights have helped us find new ways to treat cancer through a better understanding of cancer biology and specific genes that may drive tumor development. The advances achieved have not happened in silos – they are a result of multiple stakeholders with diverse backgrounds working closely together to share insights, challenge the status quo and achieve a common purpose.
However, cancer is a complex disease and despite treatment progress made over the past few decades, survival rates for many tumor types continue to be low., We must push science even further to increase these numbers. AstraZeneca and Daiichi Sankyo have a shared commitment to drive continued innovation for patients with cancer through our own collaboration. It is this shared commitment that brought our two companies together in the first place. Now, we can leverage the strengths of both companies and do more together than either of us could do alone.
To echo José’s sentiments, it is about uniting for a common purpose: patients. By putting the patient first and recognizing the current gaps in treatment, we can mobilize the best scientific minds around the world – across organizations and institutions – to truly innovate.
As our understanding behind the biology of cancer evolves and scientific technology becomes more sophisticated, the level of collaboration required to optimize new research increases. The ambition in our collaboration is only possible through close trust and alignment across the entirety of our two companies. Joining forces to combine the energy, power and expertise of our teams is how we will continue to accelerate progress in advancing treatment.
Q: Why the focus on HER2 targetable cancers?
In the early 1980s, researchers discovered that the overexpression or amplification of the HER2 gene played an important role in the growth and progression of some cancers. HER2 is now a well-established therapeutic target for patients with breast and gastric cancers. Medicines that are directed against HER2 have transformed treatment for these cancer types and improved outcomes for patients. In breast cancer, where HER2 was first researched, improvements in HER2 directed therapies have substantially improved life expectancy.,
However, despite these important scientific advancements, there are still patients with breast and gastric cancers whose disease does not respond to currently available treatment or who eventually become resistant to available treatments. In gastric cancer, the third-leading cause of cancer mortality worldwide with a five-year survival rate of 5% for metastatic disease, approximately one in five patients are HER2 positive.,, Yet, there is only one approved HER2-targeted therapy, and once patients progress on this, it has not shown any further benefit and there are no other approved HER2-targeting medicines.
There is where our collaboration is focused – on delivering continued progress in HER2 treatment.
By working together to tackle these unmet medical needs, we have the potential to provide more and better options for patients, transforming the HER2 landscape even further.
Over the years, our understanding of HER2 biology has evolved. We now know that HER2 may play a role in other forms of cancers, beyond breast and gastric, such as lung and colorectal cancers.
However, to date, HER2 directed therapies have not had much success outside of breast and gastric cancers. As such, we are working together to further investigate the possibility of HER2 as a therapeutic target for these other cancer types where there are no approved treatments that target HER2.
Q: What are you most excited about with this collaboration?
Our research is helping to increase understanding and awareness around HER2 targetable tumors, including the importance of biomarker testing across cancer types. We are also challenging ourselves to transform the status quo when it comes to classifying HER2 status and understanding the delicate and fascinating pharmacology of antibody-drug conjugate (ADC) targeting.
In breast cancer, although only approximately 15-20% express high-enough levels to be considered HER2-positive, and are therefore eligible for HER2-targeted medicines, cells labelled as HER2-negative can still express the protein., Patients who do not have HER2 positive tumors are currently classified as HER2 negative and are treated according to their hormone receptor status.
What if HER2 disease included patients with lower levels of HER2 overexpression? Or if we stopped thinking about HER2 status as a binary classification of positive and negative but more as a spectrum like we do with other biomarkers in oncology? And perhaps HER2 positivity is not the same across tumor types? And perhaps in addition to HER2 expression, which is measured by quantifying the number of HER2 receptors on the surface of the cancer cell, the presence of a HER2 gene mutation is more important in certain disease contexts? We are working hand in hand to answer some of these questions and explore how we can challenge the way we have thought about HER2 status for decades.
Without this critical thinking, innovation, collective wisdom, exploration and action, we would not be able to innovate – and by doing it together, we can hopefully evolve the science with greater speed and efficiency.
In my career as a cancer researcher and treating physician, I have seen the positive impact scientific innovation can have on patients’ lives. Understanding the role of HER2 in breast cancer radically changed the prognosis for patients with HER2 positive disease.
I am confident that with our unwavering scientific drive and commitment to improving the lives of patients, together we can further transform the treatment paradigm for even more patients with HER2 targetable cancers.
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 Bray F, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: Cancer J. Clin 2018;68:394-424.
 NCCN Guidelines® Gastric Cancer. Version 2.2020. May 13, 2020: MS-21-32.
 Schalper KA, et al. A retrospective population-based comparison of HER2 immunohistochemistry and fluorescence in situ hybridization in breast carcinomas: impact of 2007 American Society of Clinical Oncology/College of American Pathologists criteria. Arch Pathol Lab Med. 2014 Feb;138(2):213–219.
 American Cancer Society. Breast Cancer Overview. 2016.