The timeline featured below encapsulates the progress made in the treatment of renal cell carcinoma (RCC) since 1992 when options for therapy were not only limited but associated with toxicity that deterred many patients from accepting available regimens, including interleukin-2 (IL-2) and interferon. The slide developed by James Hsieh, MD, who directs the Memorial Sloan Kettering’s Translational Kidney Cancer Research Program, dramatically illustrates how far and where new directions in therapy have gone. We have seen at various points in the timeline how management strategies have ushered in what might be called “new eras” in treatment.
And, yet, as good as this timeline is in chronicling the advances made in the treatment of the disease, it is important to consider the twists and turns within these 25 years, the expectations raised by innovative approaches to the disease and yes, the setbacks and disappointments after the life cycle of various drugs revealed how challenging RCC remains and why we need to address more pathways to improve progression-free survival and overall survival. As we embark on our 15th year of publication, another era in treatment looms.
So much of the progress noted has been achieved within the years of this journal’s publication, beginning in 2003. The approvals of checkpoint inhibitors and the hopeful signs generated by the CABOSUN and S-TRAC trials delineated in this issue also suggest more questions raised by Dr Hsieh’s slide presented at the recent 15th International Kidney Cancer Symposium. For example, will the new focus on immunotherapy fulfill its promise? When and to what extent will vaccine therapies be able to put their stamp on personalized medicine in kidney cancer?
Perhaps timelines such as this are unintentionally deceptive. By breaking up the advances in treatment into convenient and easily visualized points, timelines seem to suggest that we have proceeded at nearly “warp speed” toward new treatments, some even considered revolutionary until patterns of resistance and the re-emergence of disease prove otherwise. But everyone knows the progress is painstakingly incremental.
Nevertheless, it is exciting to see in graphic form how the strategies have emerged over the years, from the first immunotherapies back in 1992, to the introduction of vascular endothelial growth factor (VEGF) inhibitors, mammalian target of rapamycin (mTOR) inhibitors, the tyrosine kinase inhibitors (TKIs) and the checkpoint or PD-1 inhibitors. Perhaps, the next timeline will even incorporate vaccine approaches still under investigation. As accurate as the timeline is in chronicling the expansion of the spectrum of therapy, it might be considered somewhat deceptive because within it, numerous approaches to sequential and combinatorial uses are not apparent. And these strategies—although not apparent in the timeline—have been a critical part of extending progression-free survival.
As the timeline suggests, we have moved from the “Dark Age” to the “Modern Age,” to what Dr Hsieh calls the “Golden Age.” We applaud his optimism and hope that the so-called Golden Age will usher in even more innovative therapies with a more favorable prognosis for our patients.
Robert A. Figlin, MD