targeted therapies

GUSTAVE ROUSSY AT THE ASCO
PRESS RELEASE
29
TH
MAY
02
ND
JUNE
2015
TARGETED THERAPIES
www.gustaveroussy.fr/asco2015
Press release
Gustave Roussy at the 51th Congress of the American Society of Clinical Oncology
TARGETED THERAPIES
AS MONOTHERAPY OR IN
EFFECTIVE COMBINATIONS
IN VARIOUS CONDITIONS
Four oral communications on targeted therapies were
given at the 51st ASCO Conference. Three of these were
at the session devoted to lung cancer on 31st May and the
fourth was in a session on sarcomas on 1st June.
Professor Jean-Charles Soria, head of the DITEP
department, presented the results of two studies. One
of these was about LUX-Lung 8, the largest randomised
study on second-line treatment of squamous cell lung
carcinoma. This phase III trial compared the effectiveness
of two targeted therapies, afatinib and erlotinib, as
second-line therapy. The second study showed the
efficacy of a 3rd generation EGFR inhibitor in non-small
cell lung cancer with EGFR mutation.
Dr David Planchard, pneumo-oncologist in the Gustave
Roussy Department of Medical Oncology, reported the
initial results of a phase II study on the effectiveness
of combined dabrafenib-trametinib therapy in B-RAF
mutated lung carcinoma.
Dr Olivier Mir, oncologist and pharmacologist in the
Gustave Roussy Department of Medical Oncology,
presented promising results from the REGOSARC study,
a phase II randomised clinical trial testing regorafenib in
patients with soft tissue sarcomas.
ASCO
2015
Flash and find
#8002
1. Afatinib (A) vs erlotinib (E) as
second-line therapy of patients
(pts) with advanced squamous
cell carcinoma (SCC) of the
lung following platinum-based
chemotherapy: overall survival
(OS) analysis from the global phase
III trial LUX-Lung 8 (LL8).
Jean-Charles Soria, Enriqueta Felip,
Manuel Cobo, Shun Lu, Konstantinos
N. Syrigos, Ki Hyeong Lee, Erdem
Goker, Vassilis Georgoulias, Wei
Li, Dolores Isla, Salih Zeki Guclu,
Alessandro Morabito, Young Joo Min,
Andrea Ardizzoni, Shirish M. Gadgeel,
Bushi Wang, Vikram K. Chand,
Glenwood D. Goss
III COMPARING TWO
SECOND-LINE TARGETED
THERAPIES
Squamous cell carcinoma is one of
the non-small cell cancers of lung.
Therapeutic options for patients at
an advanced stage after first-line
platinum-based chemotherapy are
limited. Afatinib and erlotinib are
agents which target the signalling
pathways involved in oncogenesis,
especially in this condition and
erlotinib is currently one of the
standard drugs for it.
The phase III open, randomised
LUX-Lung 8 trial presented by
Professor Jean-Charles Soria,
head of the DITEP department,
compared the effects of afatinib
to those of erlotinib on disease
progression-free and overall
survival in patients with squamous
cell carcinoma. These patients
were in therapeutic failure after
platinum-based chemotherapy.
The results showed that afatinib
was superior to erlotinib with
a 19% reduction in the risk of
progression and also a reduction
in the risk of death, combined with
better quality of life associated with
the better responses.
III PROOF OF EFFICACY OF
A 3RD GENERATION EGFR
INHIBITOR IN LUNG CANCER
In a phase I/II study, Professor
Jean-Charles Soria, head of the
DITEP department, reported
encouraging results with the use
of a 3rd generation EGFR inhibitor
(rociletinib) in patients with nonsmall cell lung cancer carrying
the T790M mutation, who had
previously been treated with one or
more other EGFR inhibitors.
456 patients participated in this
study. The results presented
showed an objective response
rate of 60% and a rate of 90% for
tumour control. The progressionfree survival period was 10.3
months. This study also showed
that the T790M mutation may be
detected in plasma. When this
was the case, the response rate
was 57%. The most frequently
observed side effects affected
less than 15% of patients. These
mainly comprised hyperglycaemia,
diarrhoea, nausea, fatigue and
reduction in appetite.
III COMBINED
TARGETED THERAPIES
Dr David Planchard, pneumooncologist in the Gustave Roussy
Department of Medical Oncology
presented the initial results of a
phase II clinical trial evaluating
the efficacy and adverse event
profile of combined dabrafenibtrametinib in patients with nonsmall cell lung cancer bearing
the BRAF V600E mutation
(around 2% of lung cancer). Both
of these targeted drugs act on
the same intracellular tumour
proliferation pathway but at 2
different points. Dabrafenib is
a very specific inhibitor of the
mutated BRAF-V600E protein,
while trametinib is a specific
inhibitor of the MEK protein.
Both drugs are taken orally, once
daily for trametinib and twice
daily for dabrafenib.
Two years ago at ASCO Dr
Planchard had already reported
very promising results for
monotherapy with dabrafenib in
bronchogenic carcinoma with
the BRAF-V600E mutation, in
progression after chemotherapy.
The overall response rate was
32% and the median duration
of treatment was prolonged by
9.6 months. The current study
shows that the combination
ASCO
2015
Flash and find
#8006
2. Interim results of a phase II study
of the BRAF inhibitor dabrafenib
(D) in combination with the MEK
inhibitor trametinib (T) in patients
(pts) with BRAF V600E mutated
metastatic non-small cell lung
cancer (NSCLC).
David Planchard, Harry J.M. Groen,
Tae Min Kim, James R. Rigas, Pierre
Jean Souquet, Christina S. Baik,
Fabrice Barlesi, Julien Mazières,
Elisabeth A. Quoix, C. Martin Curtis,
Bijoyesh Mookerjee, Arundathy N.
Bartlett-Pandite, Christine Tucker,
Anthony D’Amelio, Bruce E. Johnson
Flash and find
# 8001
3. Efficacy of rociletinib (CO-1686)
in plasma-genotyped T790Mpositive non-small cell lung cancer
(NSCLC) patients (pts).
Lecia V. Sequist, Jonathan Wade
Goldman, Heather A. Wakelee, D.
Ross Camidge, Helena Alexandra Yu,
Andrea Varga, Ben Solomon, Geoffrey
R. Oxnard, Sai-Hong Ignatius Ou,
Vassiliki Papadimitrakopoulou, Bo
H. Chao, Stephen V. Liu, Karen L.
Reckamp, Alexander I. Spira, Zofia
Piotrowska, Darrin Despain, Chris
Alan Karlovich, Sergey Yurasov, JeanCharles Soria
of dabrafenib with trametinib
significantly increases
effectiveness with an objective
tumour response of 63% without
an increase in side effects
(or even a reduction in these,
notably for cutaneous effects).
The majority of side effects
are minor (grade 1 or 2), easily
controlled and in most cases not
requiring cessation of treatment
(only 6% cessation of treatment)
but only a possible reduction
in dose. This represents a real
potential therapeutic advance
for those patients with the
BRAF-V600E mutation and,
therefore, a new potential
therapeutic weapon. The final
results of this study need to be
awaited to confirm this, with
the great majority of patients
still taking the medication. The
results reported here are only
preliminary.
III TARGETED THERAPY
IN SARCOMAS
The phase II randomised
REGOSARC study has shown
promising effects of regorafenib in
patients with soft tissue sarcomas
and the side effect profile is
acceptable.
Dr Olivier Mir, oncologist and
pharmacologist in the Gustave
Roussy Department of Medical
Oncology conducted this study
for the French Sarcoma Group.
This involved 175 patients
divided into 4 arms according to
sarcoma type: leiomyosarcoma,
synovial sarcoma, liposarcoma
and other soft tissue sarcomas.
Within each cohort the patients
were randomised (1:1) to receive
regorafenib or placebo. Patients
whose disease progressed on
placebo then received regorafenib.
The results showed that in the
« other soft tissue sarcomas »
cohort there was an improvement
in disease progression-free
survival (median: 4.6 months
on regorafenib compared with 1
month on placebo). In patients
with leiomyosarcoma, regorafenib
significantly improved overall
survival (HR 0.37, i.e. a reduction
of 63% in the risk of death).
ASCO
2015
Flash and find
#10504
4. Activity of regorafenib (RE) in
leiomyosarcomas (LMS) and other
types of soft-tissue sarcomas
(OTS): Results of a double-blind,
randomized placebo (PL) controlled
phase II trial.
Olivier Mir, Thomas Brodowicz,
Jennifer Wallet, Antoine Italiano, Axel
Le Cesne, Jean-Yves Blay, Thomas
Ryckewaert, Francois Bertucci, Sophie
Piperno-Neumann, Ferdinand Ploner,
Maud Toulmonde, Julien Domont,
Esma Saada, Corinne Delcambre,
Nicolas Isambert, Stephanie Clisant
Delaine, Sophie Taieb, Elisabeth
Lindner, Bernadette Lieg-Atzwanger,
Nicolas Penel
Targeted therapies
The goal of these therapies is to target a
specific protein or biological mechanism
involved in the development of a tumour,
so as to spare healthy cells to the
maximum extent. Gustave Roussy has
now established itself as a major centre
for personalised or molecular medicine
based on a detailed analysis of a patient’s
tumour, seeking to identify genetic
abnormalities which are accessible to
targeted therapy. The Institute is now one
of the few European centres capable of
producing within two weeks a molecular
portrait to inform therapeutic decisions.
The Gustave-Roussy medical researchers reveal
their research findings in 56 presentations at the
American Society of Clinical Oncology Conference.
The ASCO scientific committee selected 22 oral
communications, 5 of which were to be presented
directly by the Institute, 7 posters for discussion,
5 of which to be presented by Gustave-Roussy, and
25 posters.
At this 51st meeting of the most important world
conference in oncology, Gustave Roussy confirms
its leading position in two therapeutic fields which
are being absorbed into day-to-day management
and are resulting in changes in practice within
the Department of Medical Oncology (DMO):
immunotherapy which is being developed in new
disease areas, and targeted therapies and novel
approaches to tumour resistance to treatment.
This 2015 meeting will also be noteworthy for
the early evaluation through phase I clinical
trials of what will become tomorrow’s therapies,
in particular within DITEP (Drug Development
Department) at Gustave Roussy.
ASCO
MAY 29TH – JUNE 2ND, 2015
51 TH CONGRESS
American Society of Clinical
Oncology (Asco, Chicago, USA,
May 29th – June 2nd 2015).
ABOUT GUSTAVE ROUSSY
About Gustave Roussy
Gustave Roussy is the first
comprehensive cancer centre
in Europe. It is a focus of
comprehensive expertise in the
cancer field, entirely dedicated to
patients. The campus houses 3,000
professional staff engaged in patient
care, research and teaching.
– www.gustaveroussy.fr
PRESS CONTACT
GUSTAVE ROUSSY :
Communication Department
Christine Lascombe
+33 1 42 11 47 05
+33 6 26 36 76 17
[email protected]
MEDIAL :
Claire Parisel
01 53 83 81 52
[email protected]
www.gustaveroussy.fr
www.gustaveroussy.fr/asco2015
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