Six hundred fifty-seven patients were enrolled and
received 1 dose of pazopanib. Median PFS and OS were
10.3 months (95% confidence interval CI, 9.2-12.0)
and 29.9 months (95% CI, 24.7 to not reached), respectively,
and the ORR was 30.3%. HRQoL showed no or
little deterioration over time. Treatment-related serious
adverse events (AEs) and AEs of special interest occurred
in 64 (9.7%), and 399 (60.7%) patients, respectively.
More patients were classified NCTE than CTE (85.2% vs.
14.8%). Efficacy of pazopanib was similar between the
two groups.
Conclusion: PRINCIPAL confirms the efficacy and
safety of pazopanib in patients with advanced/metastatic
RCC in a real-world clinical setting. Implications for
practice: PRINCIPAL is the largest (n = 657) prospective,
observational study of pazopanib in patients with advanced/
metastatic renal cell carcinoma, to the authors’
knowledge. Consistent with clinical trial results that
often contain specific patient types, the PRINCIPAL
study demonstrated that the effectiveness and safety of
pazopanib is similarly safe and effective in patients with
advanced kidney cancer in a real-world clinical setting.
The PRINCIPAL study showed that patients with
advanced kidney cancer who are treated with first-line
pazopanib generally do not show disease progression
for approximately 10 months and generally survive for
nearly 30 months.
Metastatic Chromophobe Renal Cell Carcinoma:
Presence or Absence of Sarcomatoid Differentiation
Determines Clinical Course and Treatment
Outcomes. Ged Y, Chen Y-B, Knezevic A, et al. Clin
Genitour Cancer. 2019;17:e678-e6688.
Summary: Sarcomatoid features (SF) in renal cell carcinoma
(RCC) denote poor prognosis. Data for metastatic
chromophobe RCC (ChRCC) with SF are limited. We
studied clinical outcomes and genomic features in this
setting.We performed a retrospective review of newly
diagnosed metastatic ChRCC patients; end points
included overall survival (OS), time to treatment failure
(TTF), and time to metastatic recurrence (TTR) after
nephrectomy for localized disease. A subset of patients
underwent next-generation sequencing (NGS). Outcomes
were compared using nonparametric tests. One
hundred nine patients with metastatic ChRCC were
identified including 29 with SF. Median TTR after nephrectomy
was shorter for patients with versus without
SF (2.7 months 95% confidence interval (CI), 0.7-6.9
versus 48.8 months 95% CI, 30.8-80.7, log rank
P < .001). Median TTF during first-line therapy was
shorter for patients with versus without SF (1.8 months
95% CI, 0.9-2.7 vs. 8.0 months 95% CI, 5.1-13.0;
log rank P < .001). No responses were observed in
56 Kidney Cancer Journal
6 patients treated with nivolumab including 4 with SF.
Median OS was inferior for patients with versus without
SF (38 months vs.7.5 months; hazard ratio, 4.7 95% CI,
2.7-8.2; P < .001). NGS, performed in 22 patients,
showed that 64% and 45% harbored tumor protein P53
and phosphatase and tensin homolog alterations,
respectively. Microsatellite instability high status was
identified in 3 patients.
Conclusion: Metastatic ChRCC patients with SF had
worse outcomes compared with those without SF.
Median TTR < 3 months for this subgroup supports
close surveillance after nephrectomy for localized
tumors. Lack of benefit with various systemic regimens
warrants studying underlying biology and investigating
novel agents.
Association of Systemic Inflammation Index and
Body Mass Index with Survival in Patients with
Renal Cell Cancer Treated with Nivolumab. Clin
Cancer Research. 2019 Apr 9. doi: 10.1158/1078-0432.
CCR-18-3661. Epub ahead of print De Giorgi U, Procopio
G, Giannarelli D, et al. Inflammation indexes and
body mass index (BMI) are easily evaluated, predict
survival, and are potentially modifiable. We evaluated
the potential association of inflammatory indexes and
BMI with the clinical outcome of patients with renal
cell carcinoma (RCC) undergoing immune checkpoint
inhibitor therapy.
Summary: A prospective cohort of patients with
metastatic RCC treated with nivolumab enrolled in
the Italian Expanded Access Program from July 2015
through April 2016 was examined. Reference measures
of inflammation were identified for neutrophil-to-lymphocyte
ratio (NLR) </ 3, systemic immune inflammation
index (SII) </ 1,375, and platelet-to-lymphocyte
ratio (PLR) </ 232. Patients were classified as high BMI
(25 kg/m2) versus normal BMI (<25 kg/m2). Among
313 evaluable patients, 235 (75.1%) were male, and
median age was 65 years (range, 40–84 years), with 105
(33.69%) 70 years. In univariate analysis, age, performance
status, BMI, SII, NLR, and PLR were able to predict
outcome. In multivariate analyses, SII 1,375, BMI
<25 kg/m2, and age 70 years independently predicted
overall survival OS; HR = 2.96, 95% confidence interval
(CI), 2.05–4.27; HR = 1.59, 95% CI, 1.10–2.30; and
HR = 1.65, 95% CI, 1.07–2.55, respectively). A patient
with both SII 1,375 and BMI <25 kg/m2 was estimated
to have much worse OS (HR, 3.37; 95% CI, 2.29–4.95;
P <0.0001) than a patient with neither or only one
risk factor. SII changes at 3 months predicted OS
(P <0.0001).
Conclusions: Normal BMI combined with inflammation
tripled the risk of death, suggesting that these
biomarkers are critical prognostic factors for OS in
patients with RCC treated with nivolumab. KCJ
JOURNAL CLUB
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