sults showed that most patients present with metastatic
disease, and prognosis remains extremely poor. Nephrectomy
should be considered in all patients with
acceptable surgical risk, including cytoreductive
nephrectomy in carefully selected patients with
metastatic disease.
Overweight and obesity during adolescence increases
the risk of renal cell carcinoma. Landberg A,
Fält A, Montgomery S, et al. Int J Cancer. 2019 Feb 20.
doi: 10.1002/ijc.32147.
Summary: While overweight among adults has been
linked with renal cell carcinoma (RCC) risk, little is
known about the potential influence of overweight and
obesity during adolescence. To ascertain if adolescent
body mass index is associated with subsequent risk of
RCC, we identified a cohort of 238,788 Swedish men
who underwent mandatory military conscription assessment
between 1969 and 1976 at a mean age of 18.5
years. At the time of conscription assessment, physical
and psychological tests were performed including measurements
of height and weight. Participants were followed
through linkage to the Swedish Cancer Registry
to identify incident diagnoses of RCC. The association
between body mass index (BMI, kg/m2 ) at conscription
assessment and subsequent RCC was evaluated using
multivariable Cox regression. During a follow-up of up
to 37 years, 266 men were diagnosed with RCC. We observed
a trend for higher RCC risk with increasing BMI
during adolescence, where one-unit increase in BMI
conferred a 6% increased risk of RCC (95% CI 1.01-
1.10) compared to normal weight men (BMI 18.5- < 25),
men with overweight (BMI 25- < 30) or obesity (BMI
≥30) had hazard ratios for RCC of 1.76 and 2.87, respectively.
Conclusion: The link between overweight/obesity and
RCC appears to be already established during late adolescence.
Prevention of unhealthy weight gain during
childhood and adolescence may thus be a target in efforts
to decrease the burden of RCC in the adult population.
First-line nivolumab plus ipilimumab vs sunitinib
for metastatic renal cell carcinoma: a cost-effectiveness
analysis. Wan X, Zhang Y, Tan C, et al. JAMA
Oncol. 2019 Feb 21. doi: 10.1001/jamaoncol.2018.7086.
Summary: Considering the high cost of nivolumab
plus ipilimumab, there is a need to assess its value by
considering both efficacy and cost. A Markov model
was developed to compare the lifetime cost and effectiveness
of nivolumab plus ipilimumab vs sunitinib in
the first-line treatment of mRCC using outcomes data
from the CheckMate 214 phase 3 randomized clinical
trial, which included 1096 patients with mRCC (median
age, 62 years) and compared nivolumab plus ipilimumab
vs sunitinib as first-line treatment of mRCC. In
the analysis, patients were modeled to receive sunitinib
or nivolumab plus ipilimumab for 4 doses followed by
nivolumab monotherapy. Life-years, quality-adjusted
24 Kidney Cancer Journal
life-years (QALYs), and lifetime costs were estimated, at
a willingness-to-pay threshold of $100,000 to $150,000
per QALY. Nivolumab plus ipilimumab provided an additional
0.96 QALYs, at a cost of $108,363 per QALY. Results
were most sensitive to overall survival hazard ratio
and mean patient weight (70 kg). Other variables, such
as the cost of nivolumab plus ipilimumab (mean,
$32,213.44; range, $25,770.75-$38,656.13), utility values
for nivolumab plus ipilimumab (mean, 0.82), and
proportion receiving nivolumab in sunitinib arm
(mean, 0.27), had a moderate or minor influence on
model results. Subgroup analyses demonstrated that
nivolumab plus ipilimumab was most cost-effective for
patients with programmed cell death 1 ligand 1 expression
of at least 1% ($86,390 per QALY).
Conclusion: In this model, nivolumab plus ipilimumab
was estimated to be cost-effective compared with sunitinib
for intermediate- and poor-risk patients with
mRCC at a willingness-to-pay threshold from $100,000
to $150,000 per QALY.
Avelumab plus axitinib versus sunitinib for advanced
renal-cell carcinoma. Motzer RJ, Penkov K,
Haanen J, et al. N Engl J Med. 2019 Feb 16. doi:
10.1056/NEJMoa1816047
Summary: This phase 3 trial involving previously untreated
patients with advanced RCC compared
avelumab plus axitinib with sunitinib. Patients were
randomly assigned in a 1:1 ratio to receive avelumab
(10 mg per kg) intravenously every 2 weeks plus axitinib
(5 mg) orally twice daily or sunitinib (50 mg)
orally once daily for 4 weeks (6-week cycle). Primary
end points were progression-free survival and overall
survival among patients with programmed death ligand
1 (PD-L1)-positive tumors. A key secondary end point
was progression-free survival in the overall population;
other end points included objective response and safety.
A total of 886 patients were assigned to receive
avelumab plus axitinib (442 patients) or sunitinib (444
patients). Among the 560 patients with PD-L1-positive
tumors (63.2%), the median progression-free survival
was 13.8 months with avelumab plus axitinib, as compared
with 7.2 months with sunitinib (hazard ratio for
disease progression or death, 0.61; in the overall population,
the median progression-free survival was 13.8
months, as compared with 8.4 months (hazard ratio,
0.69; 95% CI, 0.56 to 0.84; P<0.001). Among the patients
with PD-L1-positive tumors, the objective response
rate was 55.2% with avelumab plus axitinib and
25.5% with sunitinib; at a median follow-up for overall
survival of 11.6 months and 10.7 months in the two
groups, 37 patients and 44 patients had died, respectively.
Adverse events during treatment occurred in
99.5% of patients in the avelumab-plus-axitinib group
and in 99.3% of patients in the sunitinib group; these
events were grade 3 or higher in 71.2% and 71.5% of
the patients in the respective groups.
Conclusion: Progression-free survival was significantly
longer with avelumab plus axitinib than with sunitinib
among patients who received these agents as first-line
treatment for advanced renal-cell carcinoma.
JOURNAL CLUB
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