Kidney Cancer Journal 113
wo international conferences within the last three
months provided a framework to gain new insights on
late-breaking clinical data from pivotal trials and to
explore hypothesis-generating results on a broad spectrum of
potentially transformational work. This report focuses on
selected presentations at the European Society for Medical
Oncology (ESMO) 2018 Congress held in Munich and the
International Kidney Cancer Symposium held in Miami.
ESMO 2018
ESMO 2018 provided a multi-professional platform for
oncology education and exchange, and offered immense
international visibility for scientific research. This year
the Congress also featured a dedicated nursing track
through a collaboration with the European Oncology
Nursing Society (EONS). ESMO invited a universe of
oncology stakeholders: researchers, clinicians, cancer
nurses, industry partners, patient advocates and members
of the press to join for discussions on securing better
patient outcomes through access to high-quality care. In
all, more than 1,000 attended this major international
meeting.
From posters, abstracts, and presentations, these highlights
at ESMO gave attendees a renewed focus on trends
from closely watched trials and new data likely to be
covered at upcoming international meetings of the
American Society of Clinical Oncology (ASCO), including
the GU ASCO sessions in San Francisco in February and
the main ASCO event in Chicago next June. Among
selected presentations, the following abstracts and/or
posters suggest several avenues likely to be front and
center during 2019.
Highly Selective Inhibitor Aimed at Upstream Target
in VHL-Related Disease: An open-label phase 2 study to
evaluate PT2977 for the treatment of von Hippel-Lindau
disease associated renal cell carcinoma.
Hypoxia inducible factor (HIF-2 ) has been established
as an oncogenic driver in clear cell renal cell carcinoma
(ccRCC) RCC, where VHL deficiency is the underlying
genomic alteration. In this setting of VHL gene inactivation,
HIF-2 accumulates under normoxic con-ditions,
driving the expression of genes associated with progression
of ccRCC, including vascular endothelial growth
factor A (VEGFA), cyclin D1 and other factors that
contribute to tumor growth and proliferation. A phase 2
trial is accruing VHL patients over the next year and was
described during a poster session.
The open-label Phase 2 study will evaluate the efficacy
and safety of PT2977, a highly selective small molecule
inhibitor of HIF-2 , in patients with VHL disease who
have at least one measurable ccRCC (as defined by
RECIST 1.1). PT2977 will be administered orally at a
dosage of 120 mg once daily. Key inclusion criteria include
a germline VHL alteration and at least 1 measurable
solid ccRCC but no tumor >3.0 cm that requires immediate
surgical intervention. Patients may have VHL
disease-associated tumors in other organ systems. Key
exclusion criteria include prior systemic therapy for VHL
disease, an immediate need for surgical intervention,
evidence of metastatic disease, and history of a non-VHL
disease-associated invasive malignancy in the past 2
years. The primary efficacy endpoint is objective response
rate (ORR) of ccRCC tumors per RECIST 1.1. Secondary
efficacy endpoints include duration of response (DOR),
time to response (TTR), progression-free survival (PFS),
and time to surgery (TTS) for ccRCC tu-mors as well as
efficacy evaluations for non-ccRCC VHL disease-associated
tumors. Safety/toler-ability and phar-macokinetics of
PT2977 in this trial will also be eval-uated. Patient
recruitment is ongoing.
The trial will seek an answer to whether this up-stream
CONFERENCE HIGHLIGHTS
ESMO 2018, IKCS Offer Report Cards on New Hypotheses,
Real-World Data in RCC
Eric Jonasch, MD
Professor
Department of Genitourinary
Medical Oncology
Division of Cancer Medicine
Co-Chair, Renal Cancer Program
MD Anderson Cancer Center
of the University of Texas
Houston, Texas
T