Cancer Drug Development: Views from Academia

Bernardo H.L. Goulart, MD, MS, University of Washington, Seattle Cancer Care Alliance, Seattle, Washington, USA

Fellow Summary

Authored by Swetha Kambhampati

This session focused on three parts, including role of academia in drug development, partners in clinical research, and routine management of patients enrolled in clinical trials. This is a very exciting time in drug development in oncology.

The foci of academia are drug development, transforming and advancing patient care, and teaching. We should focus on trials that create hope to cure and allow patients to live longer and live better. Trials that should be avoided are those that optimize profit or have a large sample size to capture minimal differences. We should focus on developing trials that are based on sound science, have precise biomarkers, define dose with favorable toxicity profile, and optimize patient benefit.

Given that pharmaceutical companies and biotech firms have a high share of new INDs and NMEs, industry share of funding biomedical research has increased in recent years, and successful collaboration between academic institutions and pharmaceutical companies is needed.  We need to rethink the thresholds for large phase 3 trials in the area of precision oncology.

The talk gives examples of failed trials and successful studies that have led to precision therapy in pulmonary adenocarcinomas. Lung cancer trials and the use of immunotherapy are a great example of biomarker discovery and precision therapy.

There are many different current challenges and opportunities in drug development. There are booming numbers of new targets and smaller biomarker-defined populations. This has raised the need for creative trial design (umbrella and basket trials, etc.) as well as the need to rethink the utility of randomization and whether it is realistic or always necessary. Standard of care is also rapidly changing, and costs of healthcare are also increasing.

It is important to raise the bar for clinical trials by defining clinically meaningful outcomes. The talk also gives a variety of tips to develop a successful oncology drug trial program. These tips include understanding the trade-offs, building relationships, and thinking carefully before committing to a trial. The talk goes through the various types of trials, including investigator initiated, industry sponsored, and cooperative group trials and each of their advantages and disadvantages. Clinical investigators at academic institutions need to build relationships between industry and basic, translational scientists. While cooperative group trials can help fill a gap for unanswered clinical questions, participation in cooperative groups may not be very effective when you are an early investigator unless you have a mentor who is politically strong.

This is a wonderful talk that highlights the challenges in developing clinical trials and the important things to consider when designing a trial.

Fellow Summary

Authored by Jay Oza

The number of NMEs (new molecular entities) developed/approved has increased exponentially in recent years.  For example, the FDA approved 45 NMEs in 2017, of which 31% were in the field of oncology.  It is important for clinical trials to bring patients hope for cure, to live longer, and to live better.  Trials aimed to increase company benefit or physician/investigator benefit matter less.  On the other hand, trials that matter more are the ones that improve patient benefit.  Such trials are based on sound science, precise biomarkers, dose with favorable toxicity profiles, and optimization of patient benefit. 

Partnerships with industry can be instrumental for successful drug development.  Pharmaceutical industry and biotech firms have a high share of new INDs (investigational new drugs) and NMEs.  Industry share of funding biomedical research has increased in recent years (~ 50% of biomedical research is funded by industry vs. ~ 30% funded by NIH).  As an example of successful collaboration between academia and industry, Dr. Goulart presented the biomarker discovery and companion diagnostics advances in thoracic oncology (success of EGFR mutation responsiveness to gefitinib promoted/encouraged discovery of other EGFR inhibitors as well as other precision targets in lung cancer).  Development of immunotherapy and biomarkers for response (eg. PD-L1 and MSI) are other examples of successful drug/biomarker development resulting from partnership between academia and industry.

Another potential source of collaboration are the cooperative groups.  They exist because there remains a gap in that either industry does not have an incentive to answer an outstanding question, or a treatment needs to be tried in a different indication/s.  An example of a successful partnership between academia and cooperative groups is the RTOG 1016 trial which established radiation + cisplatin (as opposed to radiation + cetuximab) as the standard of care in the management of HPV positive oropharyngeal carcinoma.  (A previous trial had shown superiority of radiation + cetuximab vs. radiation alone, whereas another trial had established cisplatin + radiation as the standard of care.  However, the two regimens [radiation + cetuximab vs radiation + cisplatin] were not compared to each other). 

There are many opportunities and challenges in drug development: booming numbers of new targets, small biomarker defined populations, high costs, and rapidly changing standards of care.  There is also the need for creative trial designs (e.g., umbrella and basket trials).  We need to rethink randomization: is it always necessary? Or realistic?

Finally, an academic physician has the responsibility of management of patients enrolled in clinical trials.  This includes identifying and consenting patients and participating in regulatory affairs, which is a necessary pain.