Kidney Cancer Journal 107
MEDICAL INTELLIGENCE
Newsworthy, late-breaking information from Web-based
sources, professional societies, and government agencies
KEYNOTE-426: Pivotal Study Hits Two Benchmarks,
Improvements in PFS, OS
A pivotal phase 3 trial investigating a combination of anti-
PD-1 therapy Keytruda and Pfizer’s tyrosine kinase inhibitor
Inlyta has shown a significant benefit on both overall (OS)
and progression-free survival (PFS) in patients with kidney
cancer.
The KEYNOTE-426 reportedly met both primary endpoints
in demonstrating statistically significant and clinically
meaningful increases in OS and PFS in the first-line
treatment of advanced or metastatic renal cell carcinoma
(RCC), compared to sunitinib monotherapy.
The study also met the key secondary endpoint of
objective response rate (ORR), with significant improvements
for the Keytruda (pembrolizumab)/Inlyta (axitinib)
combination compared with sunitinib. Results for OS, PFS
and ORR were consistent regardless of PD-L1 expression
and across all risk groups, while the safety profile of the
combination “was generally consistent with that observed
in previously reported studies for each therapy,” according
to Merck.
$20 Million for Kidney Cancer Research
Congress appropriated $10 million to establish the Kidney
Cancer Research Program (KCRP) in 2017. The appropriation
was increased to $15 million for 2018, and $20 million
for 2019. The amounts were included in the passage of a
Defense Appropriations bill.
SEER-Based Study Tracks RCC Trends:
Plateau in Incidence, Decline in Mortality
Despite an overall increase in the incidence of RCC over
two decades, there has been a recent plateau in RCC
incidence rates with a significant decrease in mortality.
Investigation of incidence and mortality trends of RCC
in the US using the cell Surveillance, Epidemiology, and
End Results (SEER) database found some good news—
a plateau of cases since 2008 and a drop in mortality since
2012. The 13 SEER registries were accessed for RCC cases
diagnosed between 1992 and 2015
A total of 104,584 RCC cases were reviewed, with
47,561 deaths. The overall incidence was 11.281 per
100,000 person-years. Incidence increased by 2.421% per
year (95% confidence interval, 2.096, 2.747; P < .001) but
later became stable since 2008. However, the incidence
of clear-cell subtype continued to increase (1.449%; 95%
confidence interval, 0.216, 2.697; P = .024). RCC overall
mortality rates have been declining since 2001. However,
mortality associated with distant RCC only started to
decrease in 2012, with an annual percentage change of
18.270% (95% confidence interval, −28.775, −6.215;
P = .006).
Tivozanib, a TKI, Continues Its Comeback—
at Least in Europe
Tivozanib (Fotivda) has been included in the upcoming
European Society of Medical Oncology (ESMO) clinical
practice guidelines for advanced renal cell carcinoma
(aRCC), anticipated to be published at the end of this year.
The outline of the new proposed guidelines was presented
at the ESMO 2018 Congress in Munich and indicated that
tivozanib will be included as a first-line treatment recommendation
for aRCC clear cell histology patients. The
update will position tivozanib as a treatment standard for
good (or favorable) risk patients with a Class IIa recommendation,
and a treatment option for intermediate risk
patients with a Class IIb recommendation.
Tivozanib was originally evaluated in the TIVO-1 phase
3 trial as a first-line therapy in RCC going head to head
against sorafenib. Despite that, trial results appeared to
meet the primary end point (improvement in median
progression-free survival (PFS), approval has only been
granted by the EMEA for use in the EU. In the US, the FDA
failed to approve tivozanib given questions about the
TIVO-1 trial that includes the study’s cross-over design and
its failure to show a significant survival benefit. In a second
attempt to gain tivozanib approval in the US, AVEO has
undertaken a new phase 3 trial named TIVO-3. Like TIVO-1
the trial design is once again a head to head trial against
sorafenib, but this time in third line (failed two prior therapies)
instead of first-line patients (or those who haven’t
been previously treated). The TIVO-3 trial is now fully
enrolled and despite some delays is expected to read out
soon.
NCCN Updates Clinical Practice Guidelines
to Include New Recommendations for
Cabozantinib Tablets
The National Comprehensive Cancer Network (NCCN)
updated its Clinical Practice Guidelines to include new
recommendations for cabozantinib (CABOMETYX tablets.
With the updates, cabozantinib is recommended by the
NCCN for the treatment of advanced RCC regardless of
patient risk status (favorable-, intermediate-, and poorrisk).
Key highlights from the updated NCCN Clinical Practice
Guidelines for Kidney Cancer include:
• Cabozantinib is the only preferred tyrosine kinase inhibitor
(TKI) treatment option for first-line patients in the
poor- and intermediate-risk groups (Category 2A).
• Cabozantinib is a recommended first-line treatment option
for favorable-risk patients (Category 2B).
• The agent is the only preferred TKI treatment option for
previously treated patients (Category 1).
Cabozantinib is the only TKI indicated for the treatment
of advanced kidney cancer with NCCN-preferred status for
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