J O U R N A L C L U B
Essential Peer-Reviewed Reading in Kidney Cancer
The peer-reviewed articles summarized in this section were selected by the
Editor-in-Chief, Robert A. Figlin, MD, for their timeliness, importance, relevance,
and potential impact on clinical practice or translational research.
Comparing the relative importance of attributes of
metastatic renal cell carcinoma treatments to patients
and physicians in the United States: A Discrete-Choice
Experiment. González JM, Doan J, Gebben DJ, et al.
Pharmacoeconomics. 2018 Jun 5; doi: 10.1007/s40273-018-
0640-7.
Summary: Patients with RCC and physicians who treat
RCC completed an online discrete-choice experiment survey.
In a series of 12 questions, respondents chose between
two hypothetical treatments defined in terms of six attributes:
progression-free survival (PFS), probability of living
≥ 3 years (PL3Y), skin reactions, severity of fatigue, mode
of administration, and monthly co-payment. Treatment
choices were analyzed using a random-parameters logit
model to estimate relative preference weights for the
attribute levels and relative attribute importance. Overall,
201 patients and 142 physicians completed the survey.
For both patients and physicians, PL3Y was the attribute
with the greatest and statistically significant conditional
relative importance. Estimates of the conditional relative
importance of PFS, skin reactions, and mode of administration
for patients, and for PFS and mode of administration
for physicians, were not statistically significant. The preferences
for improvements in PFS were independent of the
level of PL3Y for both patients and physicians. Conditional
relative attribute importance varied by patient
disease stage.
Conclusion: Patients and physicians indicated that PL3Y
was the most important treatment attribute and was significantly
more important than PFS. Importance rankings
differed between physicians and patients and between all
patients and those with advanced/metastatic disease.
Clinical activity and molecular correlates of response
to atezolizumab alone or in combination with bevacizumab
versus sunitinib in renal cell carcinoma.
McDermott DF, Huseni MA, Atkins MB, et al. Nat Med.
2018 Jun; 24(6):749-757. doi: 10.1038/s41591-018-0053-3.
Epub 2018 Jun 4.
Summary: Results are from IMmotion150, a randomized
phase 2 study of atezolizumab (anti-PD-L1) alone or
combined with bevacizumab versus sunitinib in 305
patients with treatment-naive metastatic renal cell
carcinoma. Co-primary endpoints were progression-free
survival (PFS) in intent-to-treat and PD-L1+ populations.
Intent-to-treat PFS hazard ratios for atezolizumab + bevacizumab
or atezolizumab monotherapy versus sunitinib
were 1.0 (95% confidence interval (CI), 0.69-1.45) and 1.19
(95% CI, 0.82-1.71), respectively; PD-L1+ PFS hazard ratios
were 0.64 (95% CI, 0.38-1.08) and 1.03 (95% CI, 0.63-
1.67), respectively.
Conclusion: Exploratory biomarker analyses indicated
that tumor mutation and neoantigen burden were not
associated with PFS. Angiogenesis, T-effector/IFN-
response, and myeloid inflammatory gene expression
signatures were strongly and differentially associated with
PFS within and across the treatments. These molecular
profiles suggest that prediction of outcomes with anti-
VEGF and immunotherapy may be possible and offer
mechanistic insights into how blocking VEGF may
overcome resistance to immune checkpoint blockade.
Sunitinib alone or after nephrectomy in metastatic
renal-cell carcinoma. Méjean A, Ravaud A, Thezenas S, et
al. N Engl J Med. 2018 Jun 3; doi: 10.1056/NEJMoa1803675.
Summary: this study assessed the role of nephrectomy in
patients with metastatic renal-cell carcinoma who were
receiving targeted therapies. The phase 3 trial randomly
assigned, in a 1:1 ratio, patients with confirmed metastatic
clear-cell RCC at presentation who were suitable candidates
for nephrectomy to undergo nephrectomy and then
receive sunitinib (standard therapy) or to receive sunitinib
alone. Randomization was stratified according to prognostic
risk (intermediate or poor) in the Memorial Sloan
Kettering Cancer Center prognostic model. Patients
received sunitinib at a dose of 50 mg daily in cycles of 28
days on and 14 days off every 6 weeks. The primary end
point was overall survival. A total of 450 patients were
enrolled from September 2009 to September 2017. At this
planned interim analysis, the median follow-up was 50.9
months, with 326 deaths observed. The results in the
sunitinib-alone group were non-inferior to those in the
nephrectomy-sunitinib group with regard to overall
survival. The median overall survival was 18.4 months in
the sunitinib-alone group and 13.9 months in the
nephrectomy-sunitinib group. No significant differences
in response rate or progression-free survival were observed.
Adverse events were as anticipated in each group.
Conclusion: Sunitinib alone was not inferior to nephrectomy
followed by sunitinib in patients with metastatic
renal-cell carcinoma who were classified as having
intermediate-risk or poor-risk disease.
Sunitinib in patients with metastatic renal cell carcinoma:
Clinical Outcome According to International
Metastatic Renal Cell Carcinoma Database Consortium
Risk Group. Rini BI, Hutson TE, Figlin RA, et al. Clin Geni-
40 Kidney Cancer Journal
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