Jayne Gurtler Feature

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Dr. Jayne Gurtler is a member of the Education Council and serves as the Director of CME for STO. In addition, Dr. Gurtler is the long-term CME Program Editor for The Oncologist, the official journal of the society. She has 40 years of experience and numerous published articles in oncology through her work as a practitioner and researcher and she has taught at the Xavier University School of Pharmacy. STO is grateful to have her leadership to determine essential practice gaps and educational needs of learners in order to develop programming for our educational initiatives.

Who is Dr. Jayne Gurtler?

Dr. Gurtler is a medical oncologist at the East Jefferson General Hospital and Touro in Metairie, Louisiana. As a young child, Dr. Gurtler would accompany her father, a pioneer in radiation therapy, on rounds to visit with his patients. She remembers patients opening their arms to hug her and that feeling of being needed is with her today. From this early age, she was able to get a first-hand understanding of the importance of personal care and empathy, especially when treating cancer patients.

In her lengthy career, Dr. Gurtler has seen and treated some of the most indigent populations in her community. She was a part of the disaster that resulted from Hurricane Katrina. In a reflection published in The Oncologist, she illustrated how important it is to serve the community without the need for recognition. She continually strives to provide the best care to all of her patients and her passion for her craft is evident by her selflessness with her time. In addition to a full case load at her affiliated institutions, Dr. Gurtler takes time to travel to Africa, often helping with basic healthcare needs of close friends and their communities.

In addition to providing aid in Africa, Dr. Gurtler enjoys the beautiful country, animals, and nature. Many people may not know this, but she also has a tree farm in Mississippi. The farm is in part dedicated to improving streams and rivers and restoring wetlands, protecting native endangered species of plants and animals such as gopher tortoises, native trees, and pitcher plants.

"What I do is not extraordinary. In fact, it is quite ordinary." - Dr. Jayne Gurtler

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Oncology Drug Development: A Regulatory Perspective

Oncology Drug Development: A Regulatory Perspective

Tatiana Prowell, MD, US Food and Drug Administration, Silver Spring, Maryland


Fellow summary authored by Christopher Devine, MD, MBA

Dr. Prowell provided an excellent overview of the FDA’s programs that expedite the regulatory review of novel drugs:

  1. Fast Track Designation offers the lowest threshold for a drug company to clear and is based on preclinical or clinical data that demonstrate the potential to address an unmet need. It can enable rolling submission of an NDA/BLA but does not provide any major advantage since the Prescription Drug User Fee Act (PDUFA) goal date is set by the final submission date of the data package.
  2. Breakthrough Therapy Designation (BTD) is very impactful to the review process and is based on early clinical data demonstrating a meaningful advancement over standard of care. The application for BTD is ideally submitted no later than the end of Phase 2 meeting, and sponsors receive intensive guidance from FDA throughout the review process. Notably, BTD may be withdrawn if standard of care improves and the drug is no longer a meaningful advance, or if the drug’s clinical efficacy/safety data degrades during development.
  3. Priority Review enables a six-month PDUFA clock (vs. the typical Standard Review of 10 months). This designation is available for drugs that would demonstrate a significant improvement in safety/efficacy over standard of care. Marketing the drug four months earlier than usual has important financial implications for sponsors.
  4. Accelerated Approval is the approval pathway that is arguably the most complex among the four programs. This pathway allows for approval based on surrogate endpoints reasonably likely to predict clinical benefit. In oncology, for example, drugs may be approved based on single-arm trials with an overall response rate as the primary endpoint. This is much faster than running a randomized controlled trial with a primary endpoint of progression-free and/or overall survival.

There was an extensive discussion on the nuances of accelerated approval. Importantly, the clinical benefit must be confirmed in a subsequent trial, which can present enrollment challenges for randomized studies if the drug is already commercially available and known to be effective. To mitigate these challenges, companies may confirm benefit by (1) an interim analysis of a surrogate endpoint for accelerated approval in a randomized trial with confirmation of benefit at the completion of the same trial, or (2) evaluation of the drug in earlier lines of treatment to confirm accelerated approval in later lines of disease. It is also worth noting that accelerated approval must demonstrate benefit over the current standard of care, which can change during the review process. Dr. Prowell cited the example of the EMBRACE trial of eribulin in HER2+ breast cancer, the approval of which blocked the accelerated approval of T-DM1 in the same indication. Drug development is challenging because sponsors must “play to where the puck is going, not where it currently is” and this competitive intelligence is particularly relevant for accelerated approval.

The talk also focused on the role of precision medicine at the FDA, and how biomarkers are incorporated into drug development. Dr. Prowell urges sponsors to include biomarker-negative patients in trials, given sometimes unexpected findings in prior trials and the heterogeneity of biomarkers. She illustrated these points with a number of case studies and did a very nice job covering the FDA’s role in the drug development process.


New Drug Development in 2022: Progress, Challenges, and Prices

New Drug Development in 2022: Progress, Challenges, and Prices

Thomas Roberts, MD, MSocSci, Farallon Capital Management, San Francisco, California


Fellow summary authored by Christopher Devine, MD, MBA

Dr. Roberts delivered a comprehensive and timely overview of how capital allocators, regulators, and markets contribute to drug pricing and value, culminating in a discussion on the newest drug pricing provisions passed in the Inflation Reduction Act of August 2022. The presentation began with a historical perspective on drug development – notably, that the rate of FDA new drug approvals has risen substantially over time (from <15/year in the 1970s to >35/year in the 2010s) and the median time to approval has dramatically shortened in recent years (from ~2 years in 1991 to <10 months in 2017). This is due in part to FDA programs that have shortened development times (e.g. Accelerated Approval and Real-Time Oncology Review). Over time, this higher rate of drug approvals has also been accompanied by a rise in R&D spending by pharmaceutical companies, but these R&D dollars have become less productive over that same period. Dr. Roberts discussed the structural challenges of the industry that lead to these outcomes: (1) constant rate of innovation, (2) inherent risks of drug development, (3) large pharma companies struggle to innovate, (4) R&D productivity focused on small companies, (5) crowded pipelines, and (6) smaller and more targeted drug launches.

Many of these structural challenges have led to a state in which the U.S. charges substantially higher drug prices compared to the rest of the world, effectively subsidizing biotechnology R&D. Drug costs can be measured on a relatively similar scale as some of the most expensive substances on earth, and the cost per year of life saved has also risen dramatically over the past two decades. As a result, drug pricing has naturally become a flashpoint in U.S. politics, culminating most recently in the Inflation Reduction Act. This new law outlines the following major provisions:

  1. Medicare negotiation for a specified number of high-cost drugs without generic or biosimilar equivalents that are nine (small molecules) or 13 (biologics) or more years from FDA approval (excluding drugs produced by small biotech companies)
  2. Inflation rebates if drug manufacturers increase prices faster than inflation for drugs used by Medicare beneficiaries
  3. Medicare Part D out-of-pocket caps ($2,000 cap on spending)
  4. Cost sharing for insulin limited to $35 per month

These provisions are likely to decrease the number of new drugs approved over time, and may have other implications as well (e.g. manufacturers may increase drug launch prices to overcome inflation rebates). There remains a major divide between prices in the U.S. and EU, with no easy answers that do not involve stifling innovation. Potential changes in pricing models over time may be part of the answer, particularly as new classes of drugs emerge such as gene therapy and gene editing. Dr. Roberts did a terrific job introducing us to a framework for thinking about drug value and how drug pricing will continue to evolve in the future.


Career Development in Academia

Career Development in Academia

Bernardo Goulart, MD, MS, US Food and Drug Administration, Silver Spring, Maryland


Fellow summary authored by Julia Foldi, MD, PhD

Dr. Goulart summarized different career tracks in academic medicine with an emphasis on career development of junior oncologists and the academic promotion ladder. He started his presentation with an overview of his own career path, which started in academia at the University of Washington and continued at the FDA. He briefly described the academic promotion ladder, focusing on the transition to assistant professor at which point the tenure clock begins (6-7 years) followed by mandatory promotion at many institutions to associate professor, for which the requirement is “regional and emerging national recognition”.

Because the oncology workforce is aging – >20% of current oncologists are nearing retirement and only ~14% are young career oncologists below the age of 40 – there is going to be an increasing demand for oncologists. At the same time, there is also an increasing population of cancer patients due to improved treatments. As a result, there is going to be more and more pressure on oncologists, including those in academia, to work more clinically. This pressure will always have to be balanced with the requirements for scholarly activities in academia, which can create a significant strain on individuals.

What can oncology fellows do during their training to maximize their potential for an academic career? First, the research years in fellowship are very precious and should be used to think about career development. Mentorship is one of the most crucial aspects of career development at any stage but especially while in training. It is a good idea to have several mentors with different perspectives. People should limit their clinical work to 0.5-1.5 days/week depending on research interests and include a mix of general and disease specific clinics.

In terms of research in fellowship, trainees should follow the principle of practical creativity: do not expect to change the world during fellowship, but one can ask interesting research questions that are feasible and should be planned for about one year so that the results can also be written up and disseminated by the end of fellowship. Dr. Goulart had some suggestions for such feasible research projects: correlative studies from an ongoing trial; secondary analysis of a trial; pilot/proof-of-concept studies; retrospective analyses of secondary data from institutional databases, tumor registries or national surveys. In terms of research funding, every fellow should write at least one grant proposal during fellowship, which forces you to think critically about your research. People who receive a mentored K-award are more likely to go on to receive an R01 in the future (30 times more likely!). Trainees should attempt to disseminate their research findings both via presentations and manuscripts with an emphasis on manuscript writing.

Finally, Dr. Goulart left us with some thoughts on applying for our first academic jobs, focusing on the question of whether it is preferable to stay or leave our home institution. The advantages to leaving are higher pay and better start-up packages while those of staying are familiarity, cultural integration and convenience.


Science at the Interface Between the Laboratory and the Clinic

Science at the Interface Between the Laboratory and the Clinic

Ryan Corcoran, MD, PhD, Massachusetts General Hospital Cancer Center, Boston, Massachusetts


Fellow summary authored by Yuki Kagoya, MD, PhD

Dr. Corcoran talked about how to integrate laboratory and clinical research to accelerate advances based on his own experience of translational research. While the BRAF inhibitor is effective against >50% of patients with melanoma, its response rate is only about 5% for patients with colorectal cancer (CRC). Dr. Corcoran first discovered inefficient inhibition of ERK phosphorylation by BRAF inhibition alone and showed that concomitant inhibition and BRAF and MEK improved response rate against CRC. He then demonstrated feedback reactivation mechanisms of MAPK signaling pathway through EGFR limits the efficacy of BRAF-MEK cascade inhibition. These basic research findings resulted in the development of a triple blockade approach (EGFR, MEK, and BRAF inhibition). Recently, his research focused on secondary resistance mechanisms following BRAF-MAPK inhibition therapy and demonstrated the importance of liquid biopsy to identify heterogeneous resistance mechanisms. Elucidation of resistance mechanisms through cell-free DNA (cfDNA) analysis at multiple time points enabled adaptation of targeted therapy in a real-time manner. He finally discussed recent advances in detecting residual cancer using circulating tumor DNA (ctDNA). These technologies will transform the standard of care for cancer. For example, the necessity of adjuvant chemotherapy can be determined based on the results of ctDNA analysis rather than clinical staging. In summary, his lecture clearly showed how basic research can transform clinical practice. At the same time, he also demonstrated that assessing the data on clinical specimens is essential to fuel the next discovery.


Therapeutic Resistance Including Serial Biopsy, Rapid Autopsy and Blood-based Biomarkers Platforms

Therapeutic Resistance Including Serial Biopsy, Rapid Autopsy and Blood-based Biomarkers Platforms

Dejan Juric, MD, Massachusetts General Hospital Cancer Center, Boston, Massachusetts


Fellow summary authored by Jamie Schneider, MD, PhD

Dr. Dejan Juric gave a compelling presentation on therapeutic resistance, rapid autopsy, and blood-based biomarker platforms. He focused on the interplay between preclinical scientific studies and the early clinical testing space, highlighting the importance of thinking critically about the target, biomarker, and disease selection. Thought-provoking concepts were also raised around whether early-phase clinical testing should be carried out in disease-specific or disease-agnostic contexts and how to think about restricting patient populations by biomarker selection in early-phase clinical testing.

Dr. Juric emphasized that precision oncology means developing the right treatment for the right patient at the right time. In particular, he gave an update on the precision oncology efforts carried out in the space of targeting PIK3CA mutations in advanced breast cancer. PI3K signaling regulates a broad range of cellular functions and its aberrant activation is among the most common oncogenic events across cancer types.

PIK3CA mutations mimic and enhance dynamic events during natural activation of PI3K. The level of activation depends on the specific type of mutation, underscoring the need for meticulous consideration of mutation type identified by molecular genotyping panels performed on patients. For instance, certain PIK3CA mutations such as H1047R have a greater effect in changing basal activity of the target while other mutations impact different aspects of catalytic activity. He reviewed that double mutations in cis activate PIK3CA through a combination of protein disrupter membrane binder mechanisms. Preclinical data showed mammary gland-specific expression of PIK3CA H1047R mutations induce tumors in vivo, thus spurring further interest in clinical development of isoform-specific PIK3CA inhibitors for early phase clinical testing.

Dr. Juric also discussed the differential effects of PI3K inhibitors in solid tumors, highlighting the need for iterative development of increasingly select inhibitors that are isoform- or mutation-specific. He reviewed the data from pre-clinical and early clinical studies on the FDA-approved PIK3CA inhibitor alpelisib. Other PI3K small molecule inhibitors are also in development, some of which are isoform-specific against alpha or beta isoforms, and some of which are mutant-specific (e.g. H1047R). The first-in-human trial of alpelisib in PIK3CA-altered solid tumors was a basket trial with model response rates.

Dr. Juric stressed that follow-up on this initial trial was critical to understand the biology underlying why some patients did respond while others did not. He emphasized that starting with clinical annotations and moving to comparative molecular analyses was critical in identifying etiologies of why certain patients respond. His team identified that PI3K mutant tumors have complex genomic landscapes with frequent co-occurrences of multiple oncogenic drivers and that dual inhibition with an estrogen blocker was required for efficacy. Combination regimens of ER + PI3Ka inhibition with alpelisib + fulvestrant significantly enhanced response rates, prompting moving from phase 1 directly to randomized phase 3 testing in the SOLAR-1 trial. As anticipated, the SOLAR-1 trial met its primary endpoint of PFS with the combination regimen (compared to placebo + fulvestrant). Interestingly, results from this study were published around the same time that CDK4/6 inhibitors were shown to have a marked OS benefit, clouding the optimal incorporation of PI3K inhibitors in either the first-line or later. He emphasized the importance of considering how new treatments fold into the current therapeutic landscape and how the landscape changes quickly, necessitating the reworking of sequencing of treatments. More work is underway in elucidating sequencing and combinations of CDK4/6, PI3K, and mTOR inhibitors in conjunction with endocrine therapy.


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