This last year I accepted a new position at Foundation Medicine: Director of Clinical Development, Head of Real World Outcomes Research. I was able to create an eponymous team of translational and data scientists: Real World Outcomes Research (RWOR). It has been often stressed that a sign of mastery is to simplify the complex. In this theme, I seek to succinctly describe what we do, and why we are proud of our work in 2022.
In clinical research, Real World (sometimes written "Real-world") broadly refers to data that was collected outside of clinical trials, aiming to best represent standard clinical practice or standard of care. To this end, my team is privileged to work with the Clinico-Genomic Database (CGDB) that was jointly developed by Foundation Medicine and our affiliate, Flatiron Health.
Genomic, clinical, treatment, and outcomes data (i.e. what happened to patients over time) is a very powerful combination, and over 100,000 patients' worth can enable some very powerful analyses. This database is mostly used by pharmaceutical companies in several phases of drug development. My team's focus is slightly different: to generate insights that might result in better patient care through the use of currently available drugs and biomarkers. In short: we look for ways that common clinical treatment decisions in oncology might be improved with insights from this database, aiming to improve patient care in practical, direct ways.
My team communicates these insights to the scientific and medical community through peer-reviewed publications and presentations at oncology conferences. Below is a list of our peer-reviewed publications from 2022, with short summaries in my own words.
At time of writing we have three scientific manuscripts that have been accepted and will be published soon. Stay tuned! We look forward to working hard for patients in 2023.
Summary: Biomarkers commonly assessed with genomic profiling can be used to anticipate the relative effectiveness of novel hormonal agents, the most commonly used class of drugs in previously treated metastatic prostate cancer
Summary: While not many people with later stage metastatic prostate cancer have high tumor mutational burden, when they do, it likely identifies men who have improved effectiveness of currently available immunotherapy compared to standard chemotherapy.
Summary: Standard clinical features can be used to help decide whether to order liquid biopsy (blood draw) or to send in tissue in order to perform genomic profiling of tumors for men with metastatic prostate cancer.
Summary: For physicians caring for patients with metastatic prostate cancer, when deciding to send in an archival tissue specimen, or get a new one, this can be a useful guide to know for which ones the archival tissue specimen may be valid (because getting a fresh biopsy can be challenging, difficult, painful, time-consuming, and expensive).
Summary: in lung cancer care, time is of the essence, and blood-based assessments for tumor genomic profiling can be obtained quicker. However, they can sometimes have less information. Here, we quantified this delta.
Summary: In real-world settings, about 1/3 of metastatic bladder cancer patients (identified by high tumor mutational burden) may have more favorable outcomes receiving immunotherapy instead of chemotherapy as initial treatment.
Summary: we replicated follow-on analyses from clinical trials of patients with gastric cancer, observing that those with high tumor mutational burden have more favorable outcomes on immunotherapy compared to chemotherapy.
Summary: Among men with untreated metastatic prostate cancer, those whose tumors have SPOP mutations (about 10%) do exceptionally well on 2nd generation hormonal therapies, but this extreme benefit not seen with chemotherapy. Was co-presented and published at the prestigious European Society of Medical Oncology congress, where it additionally won Best Poster in its section: https://twitter.com/DrRanaMcKay/status/1568920181719838720
Uromigos review: https://twitter.com/Uromigos/status/1569009383685726221
Summary: Tumor Fraction, a biomarker that can be assessed via a blood draw, is a marker of how well a patient is doing. It at minimum applies to those with advanced breast, prostate, lung, and colorectal cancers. Future studies will more precisely inform how to use this to improve care.
Summary: While this is not a commonly used drug class to treat metastatic prostate cancer, mTOR inhibitors unfortunately do not work well in clinical practice. Best to try something else.