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.
Cabozantinib in Renal Cell Carcinoma With Brain
Metastases: Safety and Efficacy in a Real-World
Population. Peverelli G, Raimondi A, Ratta R, et al. Clin
Genitourin Cancer. 2019. May 13. pii: S1558-7673(18)
30652-9. doi: 10.1016/j.clgc.2019.05.002. Epub
ahead of print
Summary: Cabozantinib showed efficacy and manageable
toxicity in patients with metastatic renal cell carcinoma
(mRCC). This study described the safety and
efficacy of cabozantinib in mRCC patients with brain
metastases (BM) in a real-world experience. It retrospectively
collected data of patients treated with cabozantinib
within the Italian Managed Access Program.
Patients were selected for the presence of BM before the
start of treatment and for at least 1 previous tyrosine
kinase inhibitor (TKI) treatment regimen for metastatic
disease. Safety data were reported, and overall response
rate (ORR), brain-specific response, progression-free
survival (PFS), and median overall survival (OS) were
analyzed. Overall, 12 patients treated with cabozantinib
were evaluated. Any grade adverse events (AEs)
accounted for 92%, Grade 3/4 AEs rated at 36% with no
major neurological side effects. The most common AEs
included hypertension (33%), fatigue (24%), aminotransferase
elevation (25%), hypothyroidism (16%), and
gastrointestinal toxicity (16%). The ORR was 50% with
a disease control rate of 75%. All 5 patients treated with
a combined systemic and brain-directed approach
obtained intracranial disease control, without increased
toxicity. Median PFS and median OS were 5.8 and 8.8
months, respectively. Comparable safety and tolerability
results for other TKI regimens were reported from
the literature.
Conclusion: Cabozantinib showed safety, acceptable
tolerability, and promising antitumor activity in a population
of mRCC patients with BM from a real-world
experience. A combined modality approach for renal
cell carcinoma with BM, whenever feasible, could be
recommended to improve oncological outcomes.
Morphologic subtyping as a prognostic predictor for
survival in papillary renal cell carcinoma: Type 1 vs.
type 2. Wong ECL, Di Lena R, Breau RH, et al. Urol
Oncol. 2019 Jun 5. pii: S1078-1439(19)30195-4. doi:
10.1016/j.urolonc.2019.05.009. Epub ahead of print
Summary: This study evaluated outcomes of surgically
treated patients with clinically localized papillary renal
cell carcinoma (RCC) and determine if papillary RCC
subtype is associated with recurrence and survival.
This is a historical cohort study using the prospectively
maintained Canadian Kidney Cancer Information
System database between January 2011 and September
32 Kidney Cancer Journal
2018. All patients underwent partial or radical nephrectomy.
Patient, tumor, treatment, and outcomes were
compared between papillary RCC type 2 and type 1
cohorts. During the study period, 509 patients had
clinically localized papillary RCC type 2 (n = 172) or
type 1 (n = 337) histology. Sex, race, and comorbidities
were similar between groups. Pathologic stage (pT3 or
pT4), nuclear grade (3 or 4), and tumor diameter were
higher in the type 2 papillary RCC cohort (P < 0.0001).
A greater proportion of type 2 papillary RCC patients
received radical nephrectomy (42.4% vs. 24.6%,
P< 0.0001). More type 2 papillary RCC patients underwent
lymph node dissection (19.6% vs. 5.5%, P< 0.0001)
and had lymph node metastases removed during
surgery (6.4% vs. 0.6%, P= 0.103). Overall, adjusting
for age, grade, pathologic stage, positive nodes, and
tumor size, type 2 papillary RCC had worse outcomes
compared to type 1, as demonstrated by elevated
all-cause mortality (hazard ratio = 7.7 95% confidence
interval: 2.0-28.9), P=0.0027) and worse recurrence-free
survival (hazard ratio = 8.2 95% confidence interval:
3.6-19.0, P< 0.0001).
Conclusion: Patients with clinically localized type 2
papillary RCC present with higher risk disease and have
worse prognosis compared to patients with clinically
localized type 1 papillary RCC. This is reportedly the
largest cohort study comparing papillary RCC subtypes.
Prospective Observational Study of Pazopanib in
Patients with Advanced Renal Cell Carcinoma
(PRINCIPAL Study). Schmidinger M, Bamias A, Procopio
G, et al. Oncologist. 2019 Apr;24(4):491-497. doi:
10.1634/theoncologist.2018-0787.
Summary: Real-world data are essential to accurately
assessing efficacy and toxicity of approved agents in
everyday practice. PRINCIPAL, a prospective, observational
study, was designed to confirm the real-world
safety and efficacy of pazopanib in patients with advanced
renal cell carcinoma (RCC). Patients with clear
cell advanced/metastatic RCC and a clinical decision to
initiate pazopanib treatment within 30 days of enrollment
were eligible. Primary objectives included progression
free survival (PFS), overall survival (OS), objective
response rate (ORR), relative dose intensity (RDI) and its
effect on treatment outcomes, change in health-related
quality of life (HRQoL), and safety. We also compared
characteristics and outcomes of clinical-trial-eligible
(CTE) patients, defined using COMPARZ trial eligibility
criteria, with those of non-clinical-trial-eligible (NCTE)
patients. Secondary study objectives were to evaluate
clinical efficacy, safety, and RDI in patient subgroups.
J O U R N A L C L U B
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