Kidney Cancer Journal 93
Newsworthy, late-breaking information from Web-based
sources, professional societies, and government agencies
Highlights from the IKCS, Miami, November 14-16:
New Data on Combination Therapy, Potential Strategy
in Refractory RCC, and Brain Mets
More than 400 attendees gathered in Miami for the 18th
International Kidney Cancer Symposium, as key opinion
leaders presented emerging and pivotal data from an
agenda representing the most comprehensive information
available on kidney cancer. Selected highlights are covered
here. Detailed results and perspectives on the scientific
symposium are available on the Kidney Cancer Association
website.
To view slides of all presenters, please visit:
http://www.euikcs.com/kca/miami2019
To view videos of all presentations, please visit:
https://www.oncologytube.com/channel/kidneycancer
Lenvatinib and Pembrolizumab Combination
Demonstrates Clinical Activity in Metastatic Renal Cell
Carcinoma Patients Who Received Prior Immunotherapy
MIAMI—The combination of lenvatinib and pembrolizumab
demonstrates clinical activity with a promising
objective response rate (ORR) in metastatic renal cell carcinoma
(mRCC) patients who progressed on prior immunotherapy.
An interim analysis of the ongoing phase II clinical
trial (NCT02501096) was presented by Dr. Chung-Han Lee
of Memorial Sloan Kettering Cancer Center.
A total of 33 mRCC patients who received ≤2 prior systemic
therapies, including those who progressed on a prior
anti–PD-1/PD-L1 therapy, were included in the analysis.
Patients were treated with the combination of the oral
multikinase inhibitor lenvatinib 20 mg daily and the intravenous
PD-1 inhibitor pembrolizumab 200 mg every 3
weeks. The primary endpoint was ORR by week 24 of
treatment. Secondary endpoints included ORR, progression
free survival (PFS), duration of response, and safety
and tolerability. A majority of the patients (58%) were
previously treated with nivolumab/ ipilimumab (21%) or
VEGF-targeted therapy plus PD-1/PD-L1 inhibitor combinations.
Per IMDC risk criteria, 29%, 55%, and 6% of the
patients were in the favorable-, intermediate-, and
poor-risk categories, respectively.
ORR as of week 24 was 61%. The best ORR was partial
response in 64% and stable disease in 30% of the population.
PFS was 11.3 months (95% CI, 7.3–NE) per investigator
assessment using the irRECIST v1.1 definition. From a
safety and toxicity standpoint, all patients experienced at
least one treatment-related adverse event (TRAE). Grade 3
or 4 TRAEs were seen in 55% of the cohort. Most frequently
seen TRAEs were fatigue (49%), diarrhea (39%), dysphonia
(36%), stomatitis (33%), and nausea (27%). TRAEs led to the
discontinuation of lenvatinib in 21% of patients and
pembrolizumab in 18% of patients. One patient died due
to potentially treatment-related upper gastrointestinal
bleeding.
Dr Lee highlighted the promising activity of the lenvatinib
and pembrolizumab combination in mRCC patients
previously treated with immunotherapy. The adverse
event profile of the combination was considered manageable.
Dr Lee underscored that the clinical trial
(NCT02501096) is still recruiting.
Updated OS Data on Tivozanib Suggest Potential
Role in Refractory Setting, But FDA Still Unconvinced
Pending More Results
MIAMI—Updated results from the Phase 3 TIVO-3 trial
point toward a potential role for this TKI, but so far the FDA
has withheld approval pending additional results on the
use of tivozanib. Based on the data emerging from studies
of tivozanib, there is speculation that the drug may have a
role in patients previously treated with checkpoint inhibitors
as well as two VEGFR-TKIs.
As previously presented, results for the intent to treat
(ITT) population showed that tivozanib significantly improved
progression free survival (PFS), the study’s primary
endpoint, and overall response rate (ORR) compared to
sorafenib, with responses to tivozanib more durable than
sorafenib. Newly presented data include the recently announced
interim overall survival (OS) hazard ratio (HR) of
0.99 within the ITT population, as well as results from two
prespecified subgroup analyses of patients previously
treated with a checkpoint inhibitor and a VEGF-TKI, or two
VEGFR-TKIs. Superior PFS and ORR, as well as OS HRs below
1, favoring tivozanib, were observed in the prespecified
subgroups. Tivozanib was shown to have lower overall
rates of adverse events and fewer dose interruptions and
reductions versus sorafenib, indicating better patient
tolerability.
“Until the TIVO-3 trial results, limited prospective data
existed to inform sequencing of treatment after checkpoint
inhibitor therapy, the emergent standard of care in
earlier-line treatment,” said Sumanta Pal, MD, in his presentation
at IKCS. “Tivozanib’s outcomes within this population,
as well as in those receiving two prior VEGF-TKIs,
suggest an important potential role for tivozanib in the
evolving refractory advanced RCC setting. Furthermore, tivozanib’s
unique tolerability profile is potentially well
suited to an advanced setting, where many are reluctant
to accept higher rates of adverse events following multiple
courses of therapy.” AVEO plans on completing a final OS
analysis of TIVO-3 in June 2020 after a planned submission
of a new drug application to the FDA in the first quarter of
2020.
Treatment-Free Survival With and Without Toxicity
With Nivolumab and Ipilimumab in Metastatic Renal
Cell Carcinoma
MIAMI—Treatment-free survival (TFS) without toxicity, a
(continued on page 115)
MEDICAL INTELLIGENCE
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