Kidney Cancer Journal 9
MEDICAL INTELLIGENCE
Newsworthy, late-breaking information from Web-based
sources, professional societies, and government agencies
GU ASCO 2018 Report and Highlights
New information on combination therapies dominated the
agenda at this year’s GU ASCO Symposium as cliical trials
further evaluatedwhether the use of these approaches have
potential benefit in a frontline setting.
Axitinib + Pembrolizumab Is Tolerable,
Exhibits Promising Antitumor Activity in
Treatment-Naïve Patients With Advanced RCC
SAN FRANCISCO—Axitinib with pembrolizumab has been
shown to be tolerable and to exhibit promising antitumor
activity in treatment-naïve patients with advanced renal cell
carcinoma (RCC).
This outcome of an ongoing open-label phase Ib study
was reported at the 2018 American Society of Clinical Oncology
(ASCO) Genitourinary Cancers Symposium.Michael
B. Atkins, MD, of Georgetown University Lombardi Comprehensive
Cancer Center, explained that prior studies of programmed
death-1 (PD-1) checkpoint inhibitors + tyrosine
kinase inhibitors of the vascular endothelial growth factor
(VEGF) pathway have been characterized by excess toxicity,
precluding further development. Dr Atkins and colleagues
hypothesized that axitinib, a more selective VEGF-pathway
inhibitor, + pembrolizumab (anti-PD-1) would be well
tolerated and yield antitumor activity in treatment-naïve
patients with advanced RCC.
The phase Ib trial was composed of a dose-finding
phase to determine the maximum tolerated dose and dose
expansion phase. Axitinib 5 mg was administered orally
twice daily with pembrolizumab 2 mg per kg of body
weight intravenously every 3 weeks. Tumors were assessed
using Response Evaluation Criteria in Solid Tumors v1.1 at
baseline, week 12, and every 6 weeks thereafter. The primary
endpoint was dose-limiting toxicity during the first 2
cycles (6 weeks). Secondary endpoints evaluated safety,
objective response rate, progression-free survival, and
overall survival.
No unexpected toxicities were observed. A total of 3
dose-limiting toxicities were reported among the 11
patients treated in the dose-finding phase. A transient
ischemic attack was reported in 1 patient and 2 patients
received <75% of the planned axitinib dosage due to treatment
related toxicity. At the cut-off date in 2017, 25
patients were receiving study treatment. The most common
(at least 10%) grade ≥3 all-causality adverse events
included hypertension (23%), diarrhea (10%), and fatigue
(10%). The most common (>10%) potentially immunerelated
adverse events included diarrhea (29%), increased
alanine aminotransferase (17%), and aspartate aminotransferase
(13%), hypothyroidism (13%), and fatigue (12%).
The objective response rate was 73.1% . Median progression
free survival was 20.9 months. Overall survival
data were not mature after the minimum follow-up period
of 17.6 months, and 6 treatment-unrelated deaths were
reported. Dr Atkins concluded that the combination of
axitinib + pembrolizumab was shown to be tolerable and
to exhibit promising antitumor activity in treatment-naïve
patients with advanced RCC. A randomized phase III comparison
of axitinib + pembrolizumab vs sunitinib
monotherapy is underway.
An Inflammation Scoring Tool Predicts
Overall Survival in Localized Clear Cell RCC
A high-risk clear cell RCC inflammatory score has been
shown to be an independent and significant predictor of
overall survival, with comparable accuracy to accepted
prognostic tools.
This outcome of a retrospective validation study was
reported at the 2018 ASCO Genitourinary Cancers
Symposium.
Kevin Richard Melnick, DO, of Emory University School
of Medicine, explained that a previously created and analyzed
composite RCC inflammatory score composed of
preoperative serum markers was found to be a significant
and independent predictor of overall survival in RCC, with
accuracy at least as good as other established prognostic
tools. Dr Melnick and colleagues set out to validate the
prognostic significance of this novel score in a new, independent
cohort of patients with localized clear cell RCC.
The new cohort was randomly selected from a group of
patients with localized clear cell RCC, who underwent
nephrectomy from 2007 to 2017. Data for the group was
contained in the investigators’ nephrectomy database.
Biomarker composition, cut-offs, and calculations of the
RCC inflammatory score were recreated accurately from the
previous publication. The final score was the sum of points
accrued for each biomarker, ranging from 0 - 10, followed
by stratification into baseline (0), low (1 - 3), intermediate
(4 - 6), and high-risk (7 - 10) groups. Receiver-operating
characteristics and chi-square analysis were performed to
compare the prognostic ability of this novel score vs the
Stage, SIze, Grade, and Necrosis (SSIGN), UCLA Integrated
Scoring System (UISS), modified Glasgow Prognostic Score
(mGPS, and Leibovich scores. The impact on overall survival
was analyzed using multivariate logistic regression analysis.
IMotion 150: Atezolizumab Plus
Bevacizumab Shows Potential
Results from the phase II IMmotion150 study that compared
atezolizumab (Tecentriq) plus bevacizumab (Avastin)
and atezolizumab monotherapy to sunitinib (Sutent) alone
in patients with previously untreated, locally advanced or
metastatic RCC were also presented the GU ASCO meeting.
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