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.
Metastatic clear-cell renal cell carcinoma with a
long-term response to sunitinib: a distinct phenotype
independently associated with low PD-L1 expression.
Kammerer-Jacquet SF, Brunot A, Lefort M, at
al. Clin Genitorurin Cancer. 2019 Feb 4; pii: S1558-
7673(18)30716-X. doi: 10.1016/j.clgc.2019.01.014.
Summary: Long-term responders (LTRs) are defined by
at least 18 months of response to sunitinib in metastatic
clear-cell renal cell carcinoma (ccRCC). The phenotype
of these tumors has never been explored. In a
retrospective and multicenter study, 90 ccRCCs of patients
with metastatic disease were analyzed. Immunohistochemistry
(carbonic anhydrase IX, vascular
endothelial growth factor, c-MET, programmed deathligand
1 PD-L1, and PD-1) and VHL status were performed.
Progression-free survival and overall survival
were calculated from sunitinib introduction and from
progression. LTRs and their corresponding tumors were
compared with others using univariate and multivariate
analysis.
Twenty-eight patients were LTRs. They had a median
progression-free survival of 28 months vs 4 months for
other patients. Similarly, LTRs had a median overall survival
of 49 months vs 14 months, even from progression
(median, 21 vs. 7 months). They were associated
with a favorable or intermediate risk (International
Metastatic Renal Cell Carcinoma Database Consortium
model) and less liver metastasis. They experienced more
frequent complete or partial responses at the first radiologic
evaluation. The corresponding ccRCCs were associated
with less nucleolar International Society for
Urological Pathology grade 4 and hilar fat infiltration.
They were also associated with low PD-L1 expression.
Conclusion: Primary tumor characteristics of LTRs were
studied for the first time and demonstrated a different
phenotype. Interestingly, they were characterized by
low expression of PD-L1, suggesting a potentially lower
impact of targeted immunotherapy in these patients.
Cabozantinib in advanced non-clear-cell renal cell
carcinoma: a multicentre, retrospective, cohort
study. Martinez Chanzá N, Xie W, Asim Bilen M, et al.
Lancet Oncol. 2019 Feb 28. pii: S1470-2045(18)30907-0.
doi: 10.1016/S1470-2045(18)30907-0.
Summary: This study analyzed the antitumor activity
and toxicity of cabozantinib in advanced non-clear-cell
renal cell carcinoma. This was a multicenter, international,
retrospective cohort study of patients with
metastatic nccRCC treated with oral cabozantinib during
any treatment line at 22 centers: 21 in the US and
one in Belgium. The main objectives were to estimate
the proportion of patients who achieved an objective
8 Kidney Cancer Journal
response, time to treatment failure, and overall survival
after treatment. Of 112 identified patients with nccRCC,
66 (59%) had papillary histology, 17 (15%) had
Xp11.2 translocation histology, 15 (13%) had unclassified
histology, ten (9%) had chromophobe histology,
and four (4%) had collecting duct histology. The proportion
of patients who achieved an objective response
across all histologies was 30 of 112 patients. At a median
follow-up of 11 months (IQR 6-18), median time
to treatment failure was 6·7 months, median progression
free survival was 7·0 months (5·7-9·0), and median
overall survival was 12·0 months (9·2-17·0). The most
common adverse events of any grade were fatigue (58
52%), and diarrhea (38 34%). The most common
grade 3 events were skin toxicity (rash and palmar-plantar
erythrodysesthesia; five 4%) and hypertension
(four 4%). No treatment-related deaths were observed.
Across 54 patients with available next-generation sequencing
data, the most frequently altered somatic
genes were CDKN2A (12 22%) and MET (11 20%)
with responses seen irrespective of mutational status.
Conclusion: This real-world study provides evidence
supporting the antitumor activity and safety of
cabozantinib across non-clear-cell renal cell carcinomas.
Continued support of international collaborations and
prospective ongoing studies targeting nccRCC carcinoma
subtypes and specific molecular alterations are
warranted to improve outcomes across these rare diseases
with few evidence-based treatment options.
Sarcomatoid renal cell carcinoma: population-based
study of 879 patients. Alevizakos M, Gaitanidis A, Nasioudis
D, et al. Clin Genitourin Cancer. 2019 Jan 17. pii:
S1558-7673(19)30014-X. doi:10.1016/j.clgc.2019.
01.005.
Summary: This study accessed the National Cancer Institute’s
Surveillance, Epidemiology, and End Results
database (2010-2015) and extracted data on patients
with sRCC. Median, 1-, 3-, and 5-year disease-specific
survival (DSS) probabilities were estimated to evaluate
variables associated with nephrectomy and DSS. A total
of 879 patients with sRCC were identified; 60.9% patients
had stage IV disease at diagnosis, and the median
tumor size was 8.3 cm (interquartile range, 5.5-12 cm).
The 5-year DSS were 77.7%, 67.8%, 35.4%, and 3.5% for
patients with stage I, II, III, and IV disease at diagnosis,
respectively; median DSS was 9 months (interquartile
range, 4-42 months) for the entire cohort. Older age
higher tumor stage and performance of nephrectomy
were found to independently affect DSS.
Conclusion: In the largest sRCC cohort to date, the re-
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