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Cancer Drug Development: Views from Academia

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


Scholar Summary

Authored by Yi-Tsung Lu, MD, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, California, USA

In this session, Dr. Bernardo H. L. Goulart presented the perspective of an academic physician as it pertains to the development of novel therapeutics. The lecture was divided into three portions: the role of academia in drug development, industry and cooperative groups as partners in clinical research, and routine management of patients who are enrolled in clinical trials. He began by highlighting the increasing number of biologics and new molecular entities that have been developed and have subsequently received FDA approval in recent years. One of the roles of academia in cancer care is to innovate and lead investigational therapeutic trials with a focus on maximizing patient benefits. He proposed that one way to achieve this optimization is to use precise, well-selected biomarkers that can be incorporated into trials to elucidate which therapeutics can result in clinically meaningful outcomes for a given patient population. For the second portion, he began by discussing the role of industry in providing funding for biomedical research. In 2007, industry accounted for 58% of all biomedical research funding. He went on to discuss tips for developing a successful oncology drug trial program. These included understanding the tradeoffs between investigator-initiated, industry-sponsored, and cooperative group trials. In addition, he underscored the necessity of establishing and building relationships between industry and basic/translational scientists. Also, he highlighted the importance of assessing the feasibility issues and potential for accrual prior to committing to a trial. A final recommendation was to invest in an excellent research team including research coordinators, financial analysts, program managers, and regulatory affairs personnel. To conclude the lecture, he went over the basics of identifying, consenting, and enrolling patients into trials and emphasized the importance of setting up trial expectations with the patient early on in the discussions.


Scholar Summary

Authored by Tyler Stewart, MD Yale New Haven Hospital, New Haven, Connecticut, USA

Role of academia in drug development
Dr. Goulart began his discussion by emphasizing the explosion of cancer therapeutics over the last decade. He then emphasized the role of academia in drug development and how goals may align between patients, academics, and industry, and where these may differ. He emphasized that trials that matter the most should be patient-oriented, aiming to improve patient lives and potentially cure disease. These trials should be based on strong science and designed to optimize patient benefit and minimize toxicity. Further, he emphasized a healthy amount of skepticism for trials which seem to benefit investigators and drug companies more than patients, such as large trials which are likely to show minimal difference between standard of care and the investigational agent. He then listed examples of trials that in retrospect (or maybe even prospectively) should have been avoided. He noted that some of these trials have led to FDA approval of agents and benefit to drug developers but clinically have significant toxicity and minimal benefit to patients. Afterwards, he listed examples of trials which moved cancer therapy forward, including studies with osimertinib in patients with EGFR T790M mutations, the FLAURA study, which compared osimertinib to the then standard of care first line EGFR tyrosine kinase inhibitors, and Keynote 024 which tested pembrolizumab in patients with > 50% PDL1 tumor staining. All of these trials were based on science and led to significant improvements in patient outcomes. He emphasized the need for clinicians, particularly in academia, to “raise the bar” for clinical trials and meaningful outcomes, referencing the ASCO recommended targets for meaningful clinical trial goals.


Partners in clinical research
Dr. Goulart’s discussion went on to the partnership of academia and drug industry in developing cancer therapeutics (with the understanding that the goals may not always be aligned) and development of a successful research team. He discussed that industry funding for biomedical research over the last decade has been increasing and now exceeds funding from the federal government. (In 2007, 58% of the 101 billion dollars in biomedical research funding came from industry, whereas only 33% came from the federal government.) He went on to discuss the differences in industry-sponsored trials and cooperative group trials, including the funding for patients and reimbursement to academic institutions. He emphasized that the funding from industry has led to significant benefits for patients, with several new agents now FDA- approved because of industry investment. He discussed tips for developing a successful academic research program, including: 1) understanding the trade-off of different types of trials, 2) building relationships between industry, basic/translational scientists, and cooperative group colleagues, 3) carefully considering each trial before committing, and 4) investing in a complete research staff team.



Scholar Summary

Authored by Christopher LaRocca, MD City of Hope National Medical Center, Duarte, California, USA

In this session, Dr. Bernardo H. L. Goulart presented the perspective of an academic physician as it pertains to the development of novel therapeutics. The lecture was divided into three portions: the role of academia in drug development, industry and cooperative groups as partners in clinical research, and routine management of patients who are enrolled in clinical trials. He began by highlighting the increasing number of biologics and new molecular entities that have been developed and have subsequently received FDA approval in recent years. One of the roles of academia in cancer care is to innovate and lead investigational therapeutic trials with a focus on maximizing patient benefits. He proposed that one way to achieve this optimization is to use precise, well-selected biomarkers that can be incorporated into trials to elucidate which therapeutics can result in clinically meaningful outcomes for a given patient population. For the second portion, he began by discussing the role of industry in providing funding for biomedical research. In 2007, industry accounted for 58% of all biomedical research funding. He went on to discuss tips for developing a successful oncology drug trial program. These included understanding the tradeoffs between investigator-initiated, industry-sponsored, and cooperative group trials. In addition, he underscored the necessity of establishing and building relationships between industry and basic/translational scientists. Also, he highlighted the importance of assessing the feasibility issues and potential for accrual prior to committing to a trial. A final recommendation was to invest in an excellent research team including research coordinators, financial analysts, program managers, and regulatory affairs personnel. To conclude the lecture, he went over the basics of identifying, consenting, and enrolling patients into trials and emphasized the importance of setting up trial expectations with the patient early on in the discussions.



Scholar Summary

Authored by Jessica Hawley, MD Columbia University Medical Center, New York, New York, USA

Drug development in oncology is advancing at an unprecedented rate. The average number of NMEs (new molecular entities) developed this decade has increased two-fold compared to the 2000s (~4 NMEs/year in 2000s compared to ~11NMEs/year in 2010s). NME in oncology represented ~1/3 of all FDA approvals in 2017.

Academia plays a vital role in drug development, but the academic clinician’s duty is to her patients, her institution, and to the scientific community at large. Pharmaceutical companies, on the other hand, have a duty to shareholders to make a profit. This is not to suggest that pharmaceutical companies aren’t ultimately striving to alleviate suffering and disease nor that these two interests must be mutually exclusive, but drug trials ought to be shaped to serve both academia and the pharmaceutical industry’s priorities.

Academic clinicians should design and lead investigational trials for treatments that will add health care value for individual patients and populations as a whole. Likewise, they should avoid involvement in trials focusing on “me too” drugs, trials that involve many patients for incremental benefit, and trials that seek purely to optimize profit for pharmaceutical companies. Academic clinicians should help advance trials with strong scientific rationales that use precise biomarkers, optimize patient benefits, and help define doses with favorable toxicity profiles.

Dr. Goulart’s talk and slide deck highlighted examples of the sort of science and trials we, as academic investigators, should be avoiding, e.g. lack of biomarker selection, second-line trials of chemotherapy and small molecule inhibitors with incremental benefit, and trials that increase toxicity to patients without significant benefit. He additionally highlighted cases of “good science,” specifically trials that have a biomarker component and biomarkers of progression, even if those trials used an imperfect biomarker and searched for alternative biomarkers. He argued that we should move away from marginal statistically significant benefits and towards clinically meaningful outcomes for patients.

As Dr. Goulart noted, academic investigators do collaborate with pharmaceutical industry on any number of trials, given the industry’s prominent role in R&D and capital/investment. However, those relationships can and should be managed, and we should help drive and influence the trials to which we expose our patients.

Tips for developing a successful clinical drug program included: 1) knowing the trade-offs between the different types of trials (IITs, industry-sponsored, cooperative group); 2) building relationships with stakeholders; 3) carefully considering trials before committing; and 4) investing in a research staff and infrastructure for running trials. Dr. Goulart ended his talk with some practical tips on clinical trial investigation, including careful consideration of patients for trial enrollment, the actual time involved in discussing informed consent (>60 minutes), the reality of the regulatory components, and cautious optimism that patients will successfully be enrolled to study.


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