Exploring advances at the frontline of cancer research

What I will be looking for during ASCO’s virtual program this weekend.

The annual meeting of ASCO, the American Society of Clinical Oncology, in Chicago, is a great opportunity to catch up on what’s going on at the frontline of cancer research — the virtual program running May 29 - 31, 2020 is sure to deliver the same.

ASCO is the largest meeting in clinical oncology in the world, and the meeting always brings new data, studies and insights to the global oncology and research community.

I’ll be looking for examples of Human Data Science in practice — an emerging discipline that blends human health with human science, data science and enabling technologies, and offers an integrated, multidimensional approach that can help accelerate cancer research that will benefit patients and caregivers, providers, payers and health systems. See the recently published report from the IQVIA Institute Advancing Human Data Science – A New Approach to Improve Human Health Outcomes.

Specifically, I will be looking for new answers and insights to these questions:

1. What progress is being made in improving overall survival (OS) as a clinical endpoint in oncology trials?

Over the last couple of decades, surrogate endpoints, such as progression-free survival (PFS), have taken off as the predominant clinical endpoints in clinical trials as the basis for FDA approvals of new oncology drugs. While OS remains the gold-standard measure of efficacy in cancer — assessing the length of time from randomization to death from any` cause — the application of OS has become challenging. Cancer patients nowadays live longer, which complicates the measurement as patients over time may switch therapies or introduce other potentially confounding factors that may influence their outcomes. Therefore, we have seen a proliferation of surrogate endpoints in clinical trials in cancer, first and foremost PFS that measures the length of time that a patient lives with disease without it worsening, or without dying.

A number of regulatory agencies in the U.S., EU, Japan, and Canada, accept PFS as a clinical endpoint, and from January 2006 to December 2017, 133 (73.1%) of all 188 cancer drug indications approved by FDA were based on surrogate endpoints, while only 49 (26.9%) were based on OS/Quality of Life endpoints [i].

In the last several years, there have been growing concerns that surrogate endpoints may not provide a very good measure for efficacy of oncology drugs due to potential bias, particularly in open-label studies, and lack of correlation between PFS and survival. Furthermore, patients have difficulties understanding the meaning of PFS [ii] because the term PFS seems to imply that it has something to do with survival, which in reality may not be the case.

At ASCO 2020, the majority of studies referenced in ASCO’s Clinical Advances 2020 report [iii], include OS as the clinical trial endpoint, which is promising. I will be interested in assessing whether this represents a general shift towards more objective and reliable clinical endpoints.

2. What are the barriers to using molecular diagnostics and biomarkers in cancer research?

Molecular diagnostics can help with early detection of cancer, prognosis, and prediction of the efficacy of therapy. They also help determine the presence of biomarkers that can be measured from blood, urine, tissue, tumor and other samples, thus augmenting the advancement of precision medicine. Biomarkers can also facilitate identification of cancer, specifically in high-risk populations, and lead to improved survival.

Yet, incorporation of predictive biomarkers in oncology clinical trials has stagnated at less than 50% of trials. New drug approvals with biomarkers still account for only 20% of all trials [iv]. The challenges in identifying relevant biomarkers are still significant, despite considerable focus for many years. I will be looking for further understanding of the underlying reasons for this and the prospects for breakthroughs in biomarkers and associated diagnostics. These are critical links in the progression of precision medicine.

3. How does immuno-oncology therapy change the paradigm for long-term care?

As cancer patients live longer, new guidance has been developed for long-term care post treatment with immunotherapy [v]. With the growing number of patients treated and alive, issues arise relating to side-effects and long-term risks. What are we learning about optimal care, risk of relapse, subsequent treatment protocol for patients with, say metastatic melanoma treated with immunotherapy, post 3 years, 5 years, 10 years? There is still only a small amount of real-world evidence showing what’s next for surviving patients in long-term care. Without this long-term follow-up and an integrated view of the impact that co-morbidities might also have over time, we will not be able to optimize long-term patient care after treatment with immuno-oncology therapies.

4.    What is the impact of social determinants of health in cancer research?

The concept of social determinants of health has become a buzzword in the conversation about how to improve health outcomes. There is growing consensus about the critical role of social determinants of health — in other words, factors outside the traditional clinical care environment, such as economics, employment, housing, education, the environment, cultural and personal behaviors.

Social determinants of health are important in cancer research and care, so I am looking forward to learning how this perspective will be represented at ASCO. For example, what are we learning about — and how is clinical practice reflecting — how factors in clinical care intersect with other factors, such as income, employment, transportation, housing, education, the environment, etc.; or the role that social determinants play in designing clinical trials in cancer. Human Data Science offers a methodology to combine clinical advances with data science and apply them to population health. How could the application of a Human Data Science approach provide a more holistic view of what drives improved health outcomes in cancer?

5. What are the new tools that may help oncologists make decisions at the point of care?  

Clinical cancer care is more complex than ever with the rapidly expanding knowledge about the fundamental biology of cancer, the advancements in multidisciplinary treatment strategies spanning pharmacotherapy, surgery, and radiation therapy, and the advent of combination therapies. Furthermore, there is a massive proliferation of multiple data sources and a fast-moving flow of new information. AI, machine learning, and other forms of predictive analytics, have gained traction as sophisticated tools to help oncologists make better and faster decisions at the point of care to determine optimal pathways for patients.

However, evidence is needed to demonstrate the diagnostic and therapeutic utility of these new digital tools, and I’ll be interested to see if ASCO will deliver some glimpses into this promising field. For all of the knowledge that has been accumulated about cancer care, its application at the moment of the doctor-patient decision about treatment pathways determines if it results in a better outcome for that patient. Are we seeing the tools in place to ensure that happens — not only in the leading academic medical centers, but wherever those decisions are made.

6. How will clinical oncologists adjust their approach and practice in response to COVID-19?

Since this will be the first virtual ASCO, the COVID-19 pandemic will not be far from anyone’s mind. Similarly, the practical issues that clinical oncologists have had to face over the past several weeks — imposition of social distancing rules, reduced capacity in facilities to screen or treat patients, patient concerns about physical interaction with healthcare professionals and visiting facilities, etc. — will also be the subject of much discussion. While oncology has been among the least-disrupted medical specialties, the backlog of patients due for screenings, regular visits with their primary care physicians, oncologist consultations, treatment, and follow-up is growing. Responding to this mounting number of delays and deferrals — for example, over 22 million screening tests for five common tumors risking delayed or missed diagnoses for 80,000 patients [vi] — will require changes and expanded capacity in the near term. How this is planned for and executed by clinical oncologists — including how to ensure patients resume normal levels of preventive care and screenings — should be an important topic at ASCO this year and I look forward to hearing this discussed.

Look forward to staying connected to everyone and hearing your thoughts during the virtual ASCO program and beyond.