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Cabozantinib has potential
to become first-line
treatment for renal cell
carcinoma
Cabozantinib improved progression-free survival and
the response rate versus sunitinib significantly in a
phase 2 multicentre trial in patients with metastatic
renal cell carcinoma.
T
oni Choueiri, MD, of the Dana-Farber Cancer Institute, Boston, Massa-
chusetts, explained, “Unlike sunitinib, which targets vascular endothelial
growth factor receptors, cabozantinib targets tyrosine kinase enzymes.
Cabozantinib also inhibits mesenchymal-epithelial transition (MET) factor
and AXL kinase.”
Dr Choueiri asserted, “Both MET and AXL seem to be associated with tumour
progression. But more importantly, animal models showed that the development
of resistance to vascular endothelial growth factor inhibitors like sunitinib can
be mediated by AXL kinase and MET factor.”
A total of 157 patients with untreated clear cell metastatic renal cell carci-
noma of intermediate or poor risk were randomised to oral cabozantinib (60
mg once daily) or sunitinib (50 mg once daily).
Patients who received cabozantinib exhibited a 31% reduction in the median
rate of progression or death versus those treated with sunitinib (8.2 vs 5.6
months, P = 0.012). These patients also demonstrated a significantly higher
objective response rate than patients who received sunitinib (46% vs 18%).
Dr Choueiri and colleagues observed a similar rate of adverse events in
the two groups (70.5% grade 3 or higher adverse events for cabozantinib
vs 72.2% for sunitinib). The most common adverse events for both drugs
included diarrhoea, fatigue, hypertension, palmar-plantar erythrodysesthesia,
and haematological events. Sixteen patients in each group discontinued early
due to adverse events.
Good-risk patients were not included. No biological or clinical rationale would
preclude cabozantinib in good-risk patients, however.
Dr Choueiri concluded, “Cabozantinib is approved for second or later lines of
therapies (in the US), after patients have progressed on a vascular endothelial
growth factor/tyrosine kinase inhibitor, but this data shows that cabozantinib
has the potential to become a first-line standard treatment.”
Bernard Escudier, MD, of the Institut Gustave-Roussy, Paris, commented,
“For many years, sunitinib has been the most commonly used first-line stand-
ard of care for metastatic renal cell carcinoma. Recently, cabozantinib was
proven to be active second line, especially after sunitinib failure.”
He added that results of the study raise numerous questions. Among them:
•
Are the results expandable to all metastatic renal cell carcinoma patients,
including the good prognosis group?
•
Should cabozantinib become a new, first-line standard of care?
•
How do we interpret the several ongoing phase 3 first-line trials in which
sunitinib is the control arm?
Dr Escudier concluded, “While more mature data and additional studies
using cabozantinib in the first-line setting will be required, this study has
raised expectations in the treatment of metastatic renal cell carcinoma.”
Abstract 752P
Radium-223 re-treatment from an international,
prospective, open-label study in patients with castration-
resistant prostate cancer and bone metastases.
O Sartor, D
Heinrich, N Mariados, et al
•
In this study, 44 patients with CRPC with bone
metastases who progressed after initial radium-223
treatment received additional radium-223 injections. Of
these patients, 29 received all six additional injections.
After a median 6 months from last radium-223 injection,
no significant differences in treatment-emergent adverse
event incidence in the retreatment group versus the
initial treatment group were noted. Only 3 patients in
the retreatment group reported grade 3 or 4 treatment-
related adverse events. After a maximum follow-up of
11.4 months, median time to PSA progression was 2
months. Median time to alkaline phosphatase progression
was not reached after a follow-up of 12.8 months.
•
Retreatment with radium-223 was well-tolerated, with a
toxicity profile similar to that observed in ALSYMPCA.
Abstract 760P
A post hoc analysis of radiographic progression
with nonrising prostate-specific antigen in patients with
metastatic castration-resistant prostate cancer (mCRPC) in
the PREVAIL study.
AH Bryce, JJ Alumkal, A Armstrong, et al
•
This post hoc analysis included 872 chemotherapy-naive
men with mCRPC who had received enzalutamide to
identify patients with rising PSA versus non-rising PSA at
the time of radiographic progression. Non-rising PSA was
identified in 19% of the 265 patients with radiographic
progression and evaluable PSA levels. Patients with non-
rising PSA exhibited significantly shorter median PFS
compared with patients with rising PSA, although OS
was similar. Soft-tissue disease developed in 40.3% of
patients who had bone-only disease at baseline.
•
This study highlights the need to employ surveillance
imaging in addition to PSA monitoring in patients with
mCRPC, warranting further trials to evaluate the effect
of non-rising PSA on OS.
Abstract 761P
How should we treat castration-resistant
prostate cancer patients who have received androgen
deprivation therapy (ADT) plus docetaxel upfront for hormone-
sensitive disease? Mature analysis of the GETUG-AFU 15 phase
III trial.
P Lavaud, G Gravis, C Legoupil, et al
•
This retrospective study including patients with CRPC
from the GETUG-AFU 15 phase 3 trial who received
ADT or ADT plus docetaxel was conducted to investigate
activity of treatments used beyond progression. Of the 245
men who received one or more treatments at progression,
only 17% reported grade 3 or 4 events. Patients who
received ADT only had a median overall survival of 2.29
years compared with 1.97 years in patients who received
ADT plus docetaxel. Of patients receiving docetaxel-
based chemotherapy as second-line treatment who in
first-line received ADT plus docetaxel, fewer had a PSA
response, more exhibited a symptomatic response, and
overall survival was decreased compared with patients
who received docetaxel-based chemotherapy as first-line
treatment for CRPC.
•
This study demonstrated limited benefits of docetaxel
rechallenge in these patients.
ESMO 2016
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DECEMBER 2016