Dr. Brian Rini's Perspective on 25 Years of Kidney Cancer Research
This is an excerpt of an article from the 2024 IKCS: North America PROCEEDINGS, a publication of the Kidney Cancer Journal, which highlighted key research discussed at the Kidney Cancer Association’s 2024 International Kidney Cancer Symposium (IKCS): North America held in Louisville, Kentucky on November 7-9, 2024. That meeting marked the 25th anniversary of IKCS meetings hosted by the Kidney Cancer Association.
Read the full article: An Oncologist’s Perspective on Kidney Cancer Research Over the Last 25 Years by Dr. Brian Rini, MD, FASCO, Ingram Professor of Medicine at Vanderbilt University Medical Center, an oncologist and kidney cancer expert at Vanderbilt Ingram Cancer Center in Nashville, Tennessee, and member of the KCA’s Medical Steering Committee.
I saw my first kidney cancer patients as a second-year fellow at the University of Chicago exactly 25 years ago under the mentorship of Drs. Nicholas Vogelzang and Walter Stadler. From day one, I found the biology of the disease interesting, even though at the time there were almost no therapeutics and most of our patients received clinical trial therapy. I remember one early patient encounter of a young man with advanced disease. I had been in the GU clinic for several months, and entered his room with my rehearsed speech about the therapeutic options, including interferon and interleukin-2, and then launched into clinical trial options. Feeling proud that I had mastered both of those topics and de- livered them perfectly, I was quickly brought back to earth when the wife of the patient looked at me and said, “Do you mean that’s all you’ve got?”. I slithered out of the room and have used that experience and perspective to drive my own personal journey of kidney cancer drug development. I learned from Dr. Vogelzang to always appreciate and advocate for the patient perspective and to do everything possible to optimize patient outcomes.
The early days of kidney cancer saw rare, but spectacular, responses to immunotherapeutics. For many years afterward, until the advent of checkpoint inhibitors, immunotherapy clinical trials often showed anecdotal positive responses and intriguing immune activity. However, they generally lacked broad clinical effect that could significantly alter the course of the disease… Having been fortunate to be involved from the early days of TKIs, we spent time thinking about comparing these drugs and studying them in sequence and even re-challenging with drugs previously used, in large part out of desperation. In those days, biomarker development was limited, largely due to the high cost of assays like whole exome and RNA sequencing, which are now routine. While other antiangiogenic agents were tested, they never meaningfully improved VEGF TKI monotherapy. Consequently, sequential treatment became the standard of care, though it was often limited by chronic toxicity. The next pivot point in kidney cancer drug development came with the emergence of checkpoint inhibitors, building upon the success of ipilimumab in melanoma… Checkmate 214 was a landmark study establishing dual immunotherapy as a standard of care in this disease, and for the first time we started to use the word ‘cure’ in a subset of patients.
This is the reason I show up to work every day – to keep fighting for better outcomes, to keep doing difficult investigator- initiated trials, to reflect on poor outcomes to drive further research, and to hope that one day that there is indeed a world without kidney cancer.
The most recent innovation and kidney cancer drug development has been hypoxia inducible factor (HIF) inhibitors with activity in a refractory setting and an array of studies in several different settings designed to determine whether combination therapy and/or earlier use can provide greater benefit. Biomarker development will be especially key in the development of HIF inhibitors. Kidney cancer is the most biologically diverse solid tumor in my opinion, and taking advantage of indolent biology has also emerged as an option in the form of active surveillance and metastasis-directed therapy. Surgical resection of metastases has always been part of kidney cancer patient management, and more recently stereotactic body radiotherapy (SBRT) has come into common use. Rigorous prospective testing is required for proper application of the many different tools at our disposal to care for RCC patients.
Despite the 25 years of advances that I have described, there is a long way to go to cure every patient that walks in the door. We must double down our efforts to uncover novel mechanisms that can complement existing therapies, perform difficult and expensive prospective work to validate clinically useful biomarkers and understand better how to incorporate the patient voice in drug development. A dedicated and selfless effort towards mentoring the next generation of kidney cancer researchers should be our defining legacy. The most satisfying part of my job is feeling the true appreciation of patients and their families. This appreciation is not based on outcomes, but rather on participation in their journey. A few months after the passing of a young patient that I had grown especially close to, his wife wrote me a note with the following message “You gave us more time- more memories, mores stories and more love. Because of your research our kids knew their dad. They have stories to share, and lessons learned. It is all priceless.” This is the reason I show up to work every day – to keep fighting for better outcomes, to keep doing difficult investigator- initiated trials, to reflect on poor outcomes to drive further research, and to hope that one day that there is indeed a world without kidney cancer.