Kidney Cancer Journal 111
MEDICAL INTELLIGENCE
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sunitinib versus 51.3% for placebo. Median overall survival
findings were not yet mature at the time of the analysis;
however, the hazard ratio between the two arms for
survival was 1.01 (95% CI, 0.72-1.44; P = .94).
The investigator assessed median DFS in the sunitinib
arm was 6.5 years compared with 4.5 years with placebo
(HR, 0.81; 95% CI, 0.64-1.02; P = .08). In higher risk patients,
the median DFS by investigator assessment was 5.9 versus
3.9 years for sunitinib and placebo, respectively (HR, 0.76;
95% CI, 0.58-1.01; P = .06).
Tivozanib Approved in Europe for Kidney Cancer
The European Commission (EC) has approved tivozanib (Fotivda)
for the treatment of patients with advanced renal cell
carcinoma (RCC). The drug is specifically approved for the
frontline treatment of adult patients with advanced RCC
and for adults with advanced RCC who are VEGFR- and
mTOR-inhibitor mTOR-inhibitor naïve following disease progression
after 1 prior treatment with cytokine therapy.
The approval, which follows a positive recommendation
from the European Medicines Agency’s Committee for
Medicinal Products for Human Use, is based on the phase III
TiVO-1 trial, in which tivozanib reduced the risk of disease
progression or death by over 20% vs sorafenib (Nexavar) in
patients with advanced RCC who received up to 1 prior line
of therapy (excluding targeted agents). Patients assigned to
tivozanib were more likely remain on full treatment dose
(86% vs 57%; P = .001). Only 14% of patients in the experimental
arm required dose reduction due to adverse events
(AEs) compared with 43% in the sorafenib arm. Patients in
the tivozanib group were also less likely to experience AEs
usually associated with other VEGFR-TKIs including diarrhea
(23% vs 33%) and hand-foot syndrome (14% vs 54%).
Researchers at Institut Gustave Roussy are currently
evaluating tivozanib in combination with nivolumab (Opdivo)
for patients with advanced RCC in the phase I/II dose
escalation/expansion TiNivo trial. Additionally, results are
anticipated in 2018 for the pivotal TIVO-3 trial, a randomized,
controlled, multicenter, open-label study comparing tivozanib
to sorafenib in patients with refractory advanced RCC.
TIVO-3 Study Futility Analysis Completed—
No Changes to Protocol
AVEO Oncology has announced the completion of a
pre-planned futility analysis of the Phase 3 TIVO-3 trial, the
company’s randomized, controlled, multi-center, open-label
study to compare Fotivda® (tivozanib) to sorafenib in subjects
with refractory advanced renal cell carcinoma (RCC).
Based on results of the futility analysis, which was reviewed
by an independent statistician, the study will continue as
planned without modification. This analysis did not allow
for early stopping due to efficacy to assure adequate
follow-up for the key secondary endpoint of overall
survival. The pre-planned futility analysis was triggered by
the reporting of 128 progression events in early August.
Additional events were recorded as part of the data
management process leading into the futility analysis,
resulting in a revised data cut-off date for the analysis of
May 29. The Company continues to expect the TIVO-3 to
read out in the first quarter of 2018.
The TIVO-3 trial, together with the previously completed
TIVO-1 trial of tivozanib in the first line treatment of RCC, is
designed to support regulatory approval of tivozanib in the
US as a first and third line treatment for RCC. The TIVO-3
trial was designed to enroll patients with recurrent RCC who
have failed at least two prior regimens, including VEGFR-TKI
therapy (other than sorafenib). Eligible patients may also
have received checkpoint inhibitor therapy in earlier lines
of treatment. Patients are randomized 1:1 to receive either
tivozanib or sorafenib, with no crossover between arms.
The primary endpoint of the study is progression free survival.
Secondary endpoints include overall survival, overall
response rate, and safety and tolerability.
The TiNivo trial is a Phase 1/2 study of tivozanib in combination
with Bristol-Myers Squibb’s OPDIVO® (nivolumab),
an immune checkpoint, or PD-1, inhibitor, for the treatment
of RCC. The TiNivo trial is being led by the Institut Gustave
Roussy in Paris under the direction of Bernard Escudier, MD,
Chairman of the Genitourinary Oncology Committee. The
trial advanced into the Phase 2 expansion portion following
successful completion of the Phase 1 dose escalation portion.
The combination was well tolerated to the full dose
and schedule of single agent tivozanib, with no dose limiting
toxicities. The expansion portion of the trial is expected
to enroll an additional 20 subjects. Phase 1 results from the
ongoing study have been submitted for presentation at a
scientific meeting taking place in the fourth quarter.
Phase III IMmotion151 Study Shows Tecentriq
(Atezolizumab) and Avastin (Bevacizumab)
Reduced Risk of Disease Worsening or Death for
Initial Treatment of Advanced RCC
TECENTRIQ and Avastin showed improvement in investigator
assessed progression-free survival (PFS) compared
with sunitinib for patients whose disease expressed PD-L1.
Data will be discussed with health authorities globally,
including the FDA and European Medicines Agency.
Genentech has announced that the Phase III IMmotion151
study met its co-primary endpoint of investigatorassessed
progression-free survival (PFS) and demonstrated
that the combination of TECENTRIQ® (atezolizumab) and
Avastin ® (bevacizumab) provided a statistically significant
and clinically meaningful reduction in the risk of disease
worsening or death (PFS). The results were in patients
whose disease expressed the PD-L1 (programmed
death-ligand 1; PD-L1 expression ≥1 percent) protein
compared with sunitinib for first-line treatment of
metastatic renal cell carcinoma (mRCC). KCJ