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therapy plus cytoreductive surgery in patients with
metastatic RCC (Abstract 4501).
• The randomized phase III study failing to show an
improvement in disease-free survival following 52
weeks of pazopanib in patients with mRCC who
had no evidence of disease after metastasectomy
(Abstract 4502).
• The additional findings that cytoreductive nephrec-
tomy is not superior to sunitinib alone based on
either MSKCC or IMDC risk groups (Abstract 4508).
• The IMotion 151 findings showed advantages of
atezolizumab + bevacizumab vs sunitinib regardless
of PD-L1 status in patients with untreated mRCC
(Abstract 4512).
• Patient-reported outcomes in IMotion 150 sug-
gested that atezolizumab alone or with bevacizu-
mab maintained daily function with minimal
symptom interference vs sunitinib as first-line in
mRCC (Abstract 4515).
As Rana McKay, MD, highlighted in her presentation,
we have three combination therapy regimens
approved in the first-line setting:
• Nivolumab + ipilimumab (CheckMate 214)
• Pembrolizumab + axitinib (KEYNOTE-426)
• Avelumab + axitinib (JAVELIN Renal 101)
Although ASCO 2019 does not change this paradigm,
Dr McKay’s slide on the evolution of therapy
(See Figure) encapsulates how far we have come in 15
years. What will be the next step in this evolutionary
sequence as symbolized by our silhouettes? One of the
presentations at ASCO highlighted a Phase III study
comparing bempegaldesleukin (NKTR-214) plus
nivolumab to sunitinib or cabozantinib in treatment
naïve mRCC patients. The investigational agent provides
rapid activation and proliferation of CD8+ effector
T cells and natural killer cells without overacti-
vating the immune system.
How intriguing—and ironic— that this new agent
echoes certain aspects of the first drug ever approved
for RCC—high-dose IL-2 (aldesleukin, Proleukin) a
drug that predates the timeline shown above, going
back to the 1990s. The new drug, however, apparently
is not associated with the severity of side effects of IL-2.
Bempegaldesleukin has an antibody-like dosing regimen
similar to the existing checkpoint inhibitor class
of approved medicines. Could it be that to some degree
we are circling back to some of the precepts that
guided our initial selection of therapies when highdose
IL-2 was the only option? We can look forward to
how future ASCO Scientific Sessions grapple with this
and other provocative issues.
Sumanta (Monty) Pal, MD
Guest Editor
Associate Clinical Professor
Medical Oncology
City of Hope Cancer Center
Duarte, California
(Guest Editor’s Memo, continued from inside front cover)