Creating Breakthroughs in Oncology
A Conversation with Susan Galbraith of AstraZeneca
I was lucky to host Susan Galbraith, of AstraZeneca, for the most recent episode of my podcast.
The conversation focused on AstraZeneca's approach to oncology research and development, innovation, challenges, and future outlook, highlighting Galbraith's personal journey and perspective.
Main Themes and Key Ideas:
AstraZeneca's Vision and Definition of Success in Oncology R&D:
AstraZeneca's long-term vision is ambitious: to eliminate cancer as a cause of death.
Success is measured not only by high-level goals but also by tangible improvements in five-year survival outcomes in key tumour types (e.g., lung cancer, breast cancer) and the number of patients treated with AstraZeneca medicines.
Ultimately, the impact on patients' lives is the fundamental measure of success. Hearing patient stories serves as a constant motivation for the R&D team, particularly given the inherent failures in drug discovery.
Working with a diverse and bright group of people globally, both internally and externally (investigators, sites), is another core motivating factor.
Identifying Early Signals of Success in Drug Development:
Identifying early signals in phase one trials is crucial to determining if a drug is on the right path. This involves looking for results that are different from the norm.
Experience and intuition, coupled with rigorous data analysis, are vital. Qualitative insights from investigators who are directly interacting with patients provide a valuable "sense of the qualitative, what the drug is doing" that is not always captured in standard data.
The example of osimertinib (Tagrisso) is highlighted, where seeing two responses out of four patients at the first dose level in the phase one trial, when only 50% were expected to have the target mutation, was an early indicator of something special.
Patient-Centricity and Understanding the Patient Experience:
Patient-centricity is crucial, extending beyond raw survival data to understanding the patient's journey and quality of life on treatment.
Traditional adverse event criteria (like CTCAE) may not fully capture the impact of side effects on a patient's daily life.
Digital health technologies are seen as a way to gather richer data on patient experiences and adverse events, providing a more nuanced understanding.
AstraZeneca has formed a wholly owned company, Evinova, to develop patient response and remote patient monitoring tools to capture this experience.
Leveraging Technology and Data-Driven Approaches:
Significant opportunities exist in leveraging technology to advance personalized cancer therapies.
Computational pathology and AI applied to pathology imaging are set to revolutionise diagnosis and patient identification. This includes identifying actionable mutations or expressions from unstained slides, potentially increasing the number of patients who get appropriate testing.
Advances in blood-based testing (circulating tumour DNA) are expected to enable earlier diagnosis of cancer, leading to more transformative outcomes and treatment options.
Multimodal prediction models combining various data sources (symptom history, pathology, imaging) will help identify optimal treatment strategies earlier.
Technology can also assist community oncologists in navigating the increasingly diverse set of treatment options for segmented patient subgroups, based on guidelines.
Fostering a Culture of Continuous Learning and Collaboration:
Acceptance of failure as an inevitable part of the scientific process is crucial for learning and improvement.
Allowing different groups within the organization to specialize while fostering coordination and knowledge sharing across global hubs is important.
Tapping into external knowledge networks through collaborations with academic institutions, biotech, investigators, and sites globally is key.
A culture of willingness to take risks and "play" with new technologies like AI is fostered to facilitate rapid adoption and learning.
Collaboration is fundamental to drug discovery and development, extending beyond the company to external partners. Examples include collaborations that led to insights for drugs like olaparib, capivasertib, and osimertinib.
Addressing Diversity and Barriers in Clinical Trials:
Ensuring equitable representation in clinical trials is an ongoing work in progress.
Diversity action plans are in place, with the aim of enrolling patient populations that reflect those who will ultimately be treated.
Addressing socioeconomic barriers and distance from trial sites is important. Increasing community-based sites and providing training for community oncologists are key steps.
Partnerships with patient advocacy groups and direct patient recruitment vendors help increase education and awareness about clinical trials.
Providing support for travel and associated costs helps overcome barriers to participation.
Challenges and Opportunities for the Future of Oncology:
Despite inherent challenges, Galbraith is optimistic about making a fundamental difference in cancer outcomes over the next 10 years.
Opportunities lie in combining different components in regimens (e.g., antibody-drug conjugates, immuno-oncology drugs, T-cell engagers) and moving them into earlier stages of disease.
Increased availability of diagnostics will enable better targeting of treatments at the right patients and at an earlier stage.
Navigating the increasing complexity of treatment options due to the segmentation of diseases (e.g., non-small cell lung cancer) will be a challenge, where technology can help.
Advice for Early Career Researchers, Especially Women:
Be open to opportunities, as unexpected paths can lead to success, even when initial goals are not met.
Don't self-limit; instead, identify the necessary skills and experiences for desired roles and actively pursue gaining them.
Stay curious and open-minded about areas that interest you.
Build and leverage your network, as drug discovery and development is a team effort.
Personal Journey and Pivotal Moments:
Galbraith's initial plan was to train in medicine, first considering cardiology, but a rotation in oncology at Addenbrooke’s Hospital sparked her passion for the science.
A PhD at Mount Vernon Hospital and Grey Laboratory, involving lab-based and phase one trial work on a compound licensed by a pharmaceutical company (Bristol Myers Squibb), led her to consider industry.
A pivotal moment was joining BMS and seeing the drug she had worked on for five years discontinued. This led her to learn about cancer immunology, which she was initially sceptical about, ultimately leading to the in-licensing of ipilimumab (Yervoy) and a significant role in cancer immunology development.
Most Important Ideas/Facts:
AstraZeneca's stated vision is to eliminate cancer as a cause of death.
Success is fundamentally measured by the impact on patients' lives.
Early signals in phase one trials, combined with investigator insights, are crucial for rapid decision-making.
Digital health and AI, particularly in computational pathology and blood-based testing, are expected to revolutionise cancer diagnosis and treatment identification.
A culture of learning from failure, fostering specialisation with coordination across global hubs, and tapping into external networks are key to AstraZeneca's R&D approach.
Addressing diversity in clinical trials through concrete actions like increasing community-based sites and providing support for patients is a priority.
Galbraith's personal journey highlights the importance of being open to unexpected opportunities, as exemplified by her shift into cancer immunology after a setback.
The future of oncology lies in combination therapies, earlier intervention, and leveraging technology for personalised approaches, despite increasing complexity.
Staying ahead in the competitive oncology landscape requires a strong team, an environment for agile decision-making, building networks, persistence, and a commitment to "play to win."