Download the ESMO 2012 Abstract Book - Oxford Journals

Annals of Oncology
1231PD IMPACT OF CRIZOTINIB TREATMENT ON
PATIENT-REPORTED SYMPTOMS AND QUALITY OF LIFE
(QOL) IN ADVANCED ALK-POSITIVE NON-SMALL CELL
LUNG CANCER (NSCLC)
F.H. Blackhall 1 , T.L. Evans 2 , J. Han 3 , R. Salgia 4 , D. Moro-Sibilot 5 , S. Gettinger 6 ,
L. Crino 7 , K. Wilner 8 , A. Reisman 9 ,S.Iyer 10
1 Medical Oncology, The Christie NHS Foundation Trust, Manchester, UNITED
KINGDOM, 2 Medical Oncology, University of Philadelphia, Philadelphia, PA,
UNITED STATES OF AMERICA, 3 Center for Lung Cancer, National Cancer
Center, Goyang, KOREA, 4 Department of Medicine, Section of Hematology/
Oncology, University of Chicago, Chicago, IL, UNITED STATES OF AMERICA,
5 Department of Lung Cancer, CHU De Grenoble - Hôpital A. Michalon,
Grenoble, FRANCE, 6 Thoracic Oncology, Yale University School of Medicine,
New Haven, CT, UNITED STATES OF AMERICA, 7 Medical Oncology, S. Maria
della Misericordia Hospital, Perugia, ITALY, 8 Reseach and Development, Pfizer
Oncology, La Jolla, CA, UNITED STATES OF AMERICA, 9 Medical Oncology,
Pfizer Inc, New York, NY, UNITED STATES OF AMERICA, 10 Medical Oncology,
Pfizer Oncology, New York, NY, UNITED STATES OF AMERICA
Background: Crizotinib is a potent, selective, ATP-competitive ALK inhibitor
demonstrating a high response rate in advanced ALK-positive NSCLC. The effect of
crizotinib on patient-reported symptoms, functioning and QOL from PROFILE 1005
is presented.
Methods: PROFILE 1005 is an ongoing global, multicenter, open-label, single-arm,
phase II study evaluating the safety and efficacy of crizotinib (250 mg BID in 3-week
cycles) in previously treated patients with advanced ALK-positive NSCLC.
Patient-reported outcomes (PROs) were assessed as secondary endpoints using the
European Organisation for Research and Treatment of Cancer questionnaire
(EORTC-QLQ-C30) and lung cancer module (QLQ-LC13) at baseline, Day 1 of each
cycle and at end of treatment. Functioning, symptoms and global QOL were assessed
and scored on scales of 0–100. Higher scores indicate higher symptom severity or
higher functioning/QOL. Change from baseline was assessed for statistical and
clinical significance (defined as ≥10-point change from baseline).
Results: As of Jan 2012, 901 patients were evaluable for safety and 797 (88%) of
these patients had completed the entire questionnaire at baseline. The majority of
patients was female (57%), never smokers (66%), and had adenocarcinoma (92%),
with a median age of 52 years. A clinically meaningful (≥10-point) improvement
from baseline was observed early and maintained in patient-reported symptoms of
cough (Cycle 2 onwards), pain (Cycles 2 to 19), dyspnea from QLQ–C30 (Cycles 3
to 19), pain in chest (Cycles 3 to 20 except for Cycle 18), pain in arm and shoulder
(Cycles 3 to 16) and fatigue (Cycles 4 to 21). Clinically significant deterioration was
observed for constipation (Cycles 2 and 3) and diarrhea (Cycle 2 to 6, 9 and 10).
Clinically meaningful improvements were observed for physical functioning (Cycle 8
and 9), role functioning (Cycles 9 and 10), social functioning (Cycles 4 to 15, except
Cycle 12) and global QOL (Cycles 3 to 15, except Cycle 11).
Conclusion: Treatment with crizotinib in pretreated patients with advanced
ALK-positive NSCLC showed an overall positive impact on patient-reported lung
cancer symptoms and global QOL.
Disclosure: F.H. Blackhall: Advisory relationship with Pfizer. Honoraraia, research
funding and other remuneration received from Pfizer. D. Moro-Sibilot: Honoraria
received from Pfizer. K. Wilner: Employed by Pfizer as a Senior Director and has
stock ownership with Pfizer. A. Reisman: Employed by Pfizer and has stock
ownership with Pfizer. S. Iyer: Employed as a Director (Global Outcomes Research)
by Pfizer. All other authors have declared no conflicts of interest.
1232PD LUNG CANCER HARBORING HER2 MUTATION:
EPIDEMIOLOGICAL CHARACTERISTICS AND
THERAPEUTIC PERSPECTIVES
J. Mazieres 1 , S. Peters 2 , A. Cortot 3 , B. Besse 4 , F. Barlesi 5 , M. Beau-Faller 6 ,
T. Urban 7 , D. Moro-Sibilot 8 , J. Milia 1 , O. Gautschi 9
1 Department of Pneumology, CHU Toulouse - Hôpital Larrey, Toulouse,
FRANCE, 2 Oncology, Centre Hospitalier Universitaire Vaudois - CHUV,
Lausanne, SWITZERLAND, 3 Pneumology, CHU Lille, Lille, FRANCE, 4 Thoracic
Group, INSERM U981, Institut Gustave Roussy, Villejuif, FRANCE, 5 Service
d’Oncologie Multidisciplinaire et Innovations Thérapeutique, Hôpital Nord,
Marseille, FRANCE, 6 Hôpitaux Universitaires de Strasbourg et INSERM U682
Hôpital De Hautepierre Laboratoire de Biochimie et de Biologie Moléculaire,
Strasbourg Cedex, E/M Laboratoire de Biochimiee et de Biologie Moléculaire,
Hôpitaux Universitaires de Strasbourg et INSERM U682 Hôpital de Hautepierre,
Strasbourg, FRANCE, 7 Oncology Department, CHU Anger, Anger, FRANCE,
8 Cancérologie, Hôpital A. Michallon - CHU Grenoble, Grenoble, FRANCE,
9 Medizinsiche Onkologie, Luzerner Kantonsspital, Luzern, SWITZERLAND
Introduction: HER2 oncogene is a member of the EGFR family, encoding a
transmembrane receptor that drives and regulates cell proliferation. HER2 mutations
are identified in about 2% of non small cell lung cancer (NSCLC), mainly located in
exon 20, and appear to be critical for lung cancer carcinogenesis. Very scarce data
are available to define a clinical profile of the patients harboring HER2 mutated
NSCLC. We aimed to study clinicopathological characteristics and therapeutic
outcomes of patients harboring HER2 mutation in a large European series.
Results: We retrospectively identified 46 NSCLC patients diagnosed with HER2 exon
20 mutation. HER2 mutation was mainly exclusive as only one concomitant KRas
mutation was described. Our population was characterized by a median age of 60 yr
(31 to 86 yr), a high proportion of women (30 vs. 16 men, 65%), and of never
smokers (24, 52%). All tumors were adenocarcinomas (two with lepidic features).
Half of the patients had stage IV disease at the time of diagnosis. HER2 targeted
treatment was delivered after conventional chemotherapy. A total of 20 anti-Her2
treatments were evaluable. We observed 4 progressive diseases, 7 disease stabilizations
and 9 partial responses according to RECIST 1.1 (overall response rate ORR = 45%;
disease control rate DCR = 80%). Specifically, we observed a DCR of 92% for
trastuzumab-based therapies (n = 14), 100 % for afatinib (n = 3) but no response to
lapatinib (n = 2) and to a multiTKI (n = 1). Median survival was of 68.2 months and
22.9 months for respectively early stage and stage IV patients.
Conclusion: This study, the largest to date dedicated to HER2 mutated NSCLC,
reinforces the importance of an HER2 screening strategy in lung adenocarcinomas.
HER2-targeted drugs should be tested further, ideally within large collaborative
clinical trials.
Disclosure: All authors have declared no conflicts of interest.
1233PD EFFICACY AND PATIENT (PT)-REPORTED OUTCOMES
(PROS) WITH SELUMETINIB (AZD6244, ARRY-142866;
SEL) + DOCETAXEL (DOC) IN KRAS-MUTANT ADVANCED
NON-SMALL CELL LUNG CANCER (NSCLC): A
RANDOMIZED, PHASE II TRIAL
P.A. Janne 1 , A.T. Shaw 2 , J.R. Pereira 3 , G. Jeannin 4 , J.F. Vansteenkiste 5 ,
C. Barrios 6 , F.A. Franke 7 , L. Grinsted 8 , I. Smith 8 , L. Crino 9
1 Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, MA,
UNITED STATES OF AMERICA, 2 Hematology/Oncology, Massachusetts General
Hospital, Boston, MA, UNITED STATES OF AMERICA, 3 Depto de Pneumologia,
Grupo de Assistencia Médica, Sao Paulo, BRAZIL, 4 Service de Pneumologie,
Hôpital Gabriel Montpied, Clermont- Ferrand, FRANCE, 5 Respiratory Oncology
Unit (Pulmonology), University Hospital Gasthuisberg, Leuven, BELGIUM,
6 Oncology, Hospital Sao Lucas da PUC de Porto Alegre, Porto Alegre, BRAZIL,
7 Cacon, Hospital de Caridade de Ljui, Ljui, BRAZIL, 8 Oncology, Astra Zeneca,
Alderley Park, UNITED KINGDOM, 9 Department of Oncology, Hospital Santa
Maria della Misericordia, Perugia, ITALY
Objectives: This randomized, double-blind, placebo (PBO)-controlled, phase II trial
evaluated the efficacy and safety of SEL + DOC as second-line treatment for pts with
KRAS-mutant advanced NSCLC. Assessment of the prevalence, severity, and change
over time of lung cancer symptoms was an exploratory objective.
Methods: Pts with stage IIIB-IV, second-line KRAS-mutant advanced NSCLC,
received iv DOC 75mg/m 2 , and po SEL 75mg or PBO BD. PROs were assessed using
the Lung Cancer-Specific Symptom Questionnaire (LSSQ), which includes the Lung
Cancer Subscale (LCS) plus items relating to symptoms and functional activities
from the FACT-L. Pts completed the questionnaire on Day 1, and every 3 weeks
until discontinuation from study treatment, and at discontinuation.
Results: 422 pts were screened across 67 centers in 12 countries; 87 were randomized
(SEL + DOC, 44; PBO + DOC, 43). Baseline characteristics were reasonably balanced.
OS was longer for SEL + DOC vs PBO + DOC (9.4 vs 5.2 mo), but not statistically
significant (HR 0.80; 80% CI 0.56–1.14) and hazards were non-proportional. All
secondary endpoints, including response rate (37% vs 0%; p < 0.0001) and PFS (5.3
vs 2.1 mo; HR 0.58; 80% CI 0.42–0.79), were significantly improved for SEL + DOC
vs PBO + DOC. Most frequent grade 3/4 AEs were neutropenia and febrile
neutropenia. Compliance for completion of the LSSQ at baseline and at least 1
follow-up visit was 85.5%. There was a numerical improvement in the change from
baseline in the LSSQ scores with SEL + DOC compared with PBO + DOC,
throughout the assessment period. In a post-hoc analysis, the % pts with a clinically
meaningful improvement in LCS score was greater for SEL + DOC (44%) than PBO
+ DOC (24%; OR 2.50; 80% CI 1.34–4.77; 1-sided p = 0.029). The time to
deterioration of LCS score was also in favor of SEL + DOC (HR 0.33; 80% CI 0.22–
0.49; 1-sided p = 0.0002).
Conclusions: This is the first prospective study to demonstrate a clinical benefit of
targeted therapy (SEL + DOC) for pts with KRAS-mutant cancer of any type. In a
post-hoc analysis, more pts experienced clinically meaningful improvements in lung
cancer symptoms with SEL + DOC than PBO + DOC.
Disclosure: P.A. Janne: I have served as a consultant to Astra Zeneca and have been
compensated. A.T. Shaw: Research funding from Astra Zeneca and funding for costs
of clinical trials. J.F. Vansteenkiste: Dr. Vansteenkiste is the holder of the Astra
Zeneca Chair in personalized lung cancer care which provides research funding. L.
Grinsted: Lynda Grinsted is an employee of Astra Zeneca and receives stock shares. I.
Smith: Ian Smith is an employee of Astra Zeneca and receives stock. All other
authors have declared no conflicts of interest.
Volume 23 | Supplement 9 | September 2012 doi:10.1093/annonc/mds409 | ix403