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Ingelheim, GSK Biologicals (compensated). Received honoraria from all the above.
Research funding from AstraZeneca. J. O’Connell: Employed by Pfizer as Senior
Director. Holds Pfizer stock. S. Ou: Advisory relationship with Pfizer and Genentech
(compensated). Honoraria from Pfizer, Genentech and Eli Lilly. Research funding
from Pfizer. I. Taylor: Employed by Pfizer as a Senior Director. Holds Pfizer stock.
H. Zhang: Employed by Pfizer as a Senior Manager. Holds Pfizer stock.
1229PD LUX-LUNG 3: SYMPTOM AND HEALTH-RELATED QUALITY
OF LIFE RESULTS FROM A RANDOMIZED PHASE III STUDY
IN 1ST-LINE ADVANCED NSCLC PATIENTS HARBOURING
EGFR MUTATIONS
L.V. Sequist 1 , M. Schuler 2 , N. Yamamoto 3 , K.J. O’Byrne 4 , V. Hirsh 5 , T.S.
K. Mok 6 , J. Lungershausen 7 , M. Shahidi 8 , M. Palmer 9 , J.C. Yang 10
1 Medicine, Massachusetts General Hospital, Boston, MA, UNITED STATES OF
AMERICA, 2 Medicine, West German Cancer Center, University Duisburg-Essen,
Essen, GERMANY, 3 Thoracic Oncology, Shizuoka Cancer Center, Shizuoka,
JAPAN, 4 Oncology, St James’s Hospital, Dublin, IRELAND, 5 Oncology, McGill
University Health Centre, Montreal, QC, CANADA, 6 Department of Clinical
Oncology, The Chinese University of Hong Kong, Shatin, Hong Kong, CHINA,
7 Health Economics, Boehringer Ingelheim, Ingelheim, GERMANY, 8 Clinical
Research / Management, Boehringer Ingelheim, Bracknell, UNITED KINGDOM,
9 Statistics, Keele University, Keele, UNITED KINGDOM, 10 Oncology, National
Taiwan University Hospital, Taipei, TAIWAN
Background: Afatinib (A) is an oral, irreversible ErbB family blocker. LUX-Lung 3
compared A with cisplatin/pemetrexed (CP) in patients with EGFR mutation positive
lung adenocarcinoma. The primary analysis demonstrated significant improvement
in progression-free survival (PFS), with a median PFS of 11.1 months for A and 6.9
months for CP (HR = 0.58, p = 0.0004). Here, we present patient-reported
Health-related Quality of Life (HRQoL) data.
Methods: 345 patients were randomized (2:1) to receive A or CP. Symptoms and
HRQoL were measured using EORTC questionnaires (QLQ-C30/LC13) at baseline
and q3w until progression. Changes of ≥10 points were considered clinically
significant. Analyses of cough, dyspnoea and pain symptoms were pre-specified.
Time to deterioration (1st 10-point worsening from baseline) was analyzed using a
stratified log rank test. Percentage improved/worsened by ≥10 points or stable was
determined. Mean scores over time were estimated using longitudinal (mixed-effects
growth curve) models.
Results: Compliance with questionnaires was >85% over time and all patients had
low baseline symptom burden. Compared to CP, therapy with A significantly delayed
time to deterioration for cough (HR = 0.60; p = 0.0072) and dyspnoea (HR = 0.68; p
= 0.0145); results for pain trended toward A (HR = 0.82; p = 0.1913). A higher
proportion of A-treated patients had ≥10 point improvements in cough (67% vs
60%; p = 0.2444), dyspnoea (64% vs 50%; p = 0.0103) and pain (59% vs 48%; p =
0.0513), compared to CP, particularly among patients with baseline symptoms. Mean
scores over time for cough and dyspnoea also significantly favoured A. Consistent
with the safety profile of A, a higher proportion of A-treated patients had significant
worsening of symptoms of diarrhoea, sore mouth and dysphagia compared to CP.
Reported fatigue, nausea, and vomiting were significantly worse on CP. Overall,
therapy with A improved global HRQoL, physical, role and cognitive functioning
compared to CP (p < 0.05).
Conclusion: In LUX-Lung 3, prolongation of PFS on A was associated with
significant HRQoL improvement and delay of deterioration of lung cancer-related
symptoms compared to CP.
Disclosure: L.V. Sequist: Paid consultancy/advisory relationship with: Boehringer
Ingelheim, Daiichi-Sankyo, Merrimack, Clovis and Celgene; Research funding from:
Boehringer Ingelheim. M. Schuler: Paid consultancy/advisory relationship with:
Boehringer Ingelheim; Research funding from: Boehringer Ingelheim; Travel support
from: Lilly. K.J. O’Byrne: Paid consultancy/advisory relationship with: Boehringer
Ingelheim, Lilly Oncology; Honoraria from Boehringer Ingelheim, Lilly Oncology;
Research funding from Boehringer Ingelheim; Other remuneration from Boehringer
Ingelheim, Lilly Oncology. V. Hirsh: Honoraria from the Boehringer Ingelheim
Advisory Board. T.S.K. Mok: Paid consultancy/advisory relationship with and
honoraria from: AstraZeneca, Roche, Eli Lilly, Merck Serono, Eisai, BMS, BeiGene,
AVEO, Pfizer, Taiko, Boehringer Ingelheim; Research funding from: AstraZeneca. J.
Lungershausen: Employee of Boehringer Ingelheim. M. Shahidi: Employee of
Boehringer Ingelheim. M. Palmer: Consulting fee, honorarium, travel support, fees
for reviews, and payment for writing or reviewing the manuscript via N Zero 1 Ltd;
Board membership of N Zero 1 Ltd and consultancy, travel/accommodation/meeting
costs unrelated to activities listed. J.C. Yang: James Chih-Hsin Yang has received
honorarium for speech and advisory roles from Astrazeneca, Roche, Pfizer, OSI. He
was the advisor for Boehringer Ingelheim and Eli Lilly without payment. All other
authors have declared no conflicts of interest.
1230PD UPDATED RESULTS OF A GLOBAL PHASE II STUDY WITH
CRIZOTINIB IN ADVANCED ALK-POSITIVE NON-SMALL
CELL LUNG CANCER (NSCLC)
D. Kim 1 , M. Ahn 2 ,P.Yang 3 , X. Liu 4 ,T.DePas 5 , L. Crinò 6 , S. Lanzalone 7 ,
A. Polli 7 , A. Shaw 8
1 Internal Medicine, Seoul National University Hospital, Seoul, KOREA, 2 Division of
Hematology/Oncology, Department of Medicine, Sungkyunkwan University
School of Medicine Samsung Medical Center, Seoul, KOREA, 3 Department of
Internal Medicine, National Taiwan University College of Medicine, Taipei,
TAIWAN, 4 Cancer Center, 307 Hospital of the Academy of Military Medical
Sciences, Beijing, CHINA, 5 Medical Oncology Unit of Respiratory Tract and
Sarcomas, European Institute of Oncology, Milano, ITALY, 6 Department of
Medical Oncology, Ospedale Santa Maria della Misericordia, Perugia, ITALY,
7 Oncology, Pfizer, Milano, ITALY, 8 Hematology/Oncology, Department of
Medicine, Massachusetts General Hospital, Boston, MA, UNITED STATES OF
AMERICA
Background: Anaplastic lymphoma kinase (ALK) is a known oncogenic driver in
NSCLC, and approximately 5% of patients harbor ALK gene rearrangements.
Crizotinib is a first-in-class, selective small-molecule ALK inhibitor with
demonstrated clinical activity in ALK-positive NSCLC. PROFILE 1005 is a global,
multicenter, open-label, single-arm phase II study evaluating the safety and
efficacy of crizotinib in previously treated patients with ALK-positive advanced
NSCLC.
Methods: Crizotinib 250 mg was administered BID to patients with ALK-positive
advanced NSCLC who had received ≥1 chemotherapy for locally advanced/
metastatic disease, including those with treated brain metastases. Most patients had
centrally confirmed ALK-positivity by break-apart fluorescence in-situ hybridization,
defined as ≥15% of tumor cells with split signals. Disease response was evaluated by
RECIST 1.1 every 6 weeks.
Results: As of January 2012, 901 patients had been dosed. The first 261 patients
who had enrolled and started crizotinib by February 2011, with a median
duration of treatment of 48 weeks, were considered to be the mature population.
Demographic, exposure, and efficacy results in both the overall and mature
populations are provided in the table. Among all 901 patients, 15% discontinued
treatment due to adverse events (AEs) and 10% had a dose reduction due to an
AE. The most frequent AEs of any cause were vision disorder (54%), nausea
(51%), diarrhea (44%), vomiting (44%), and constipation (37%), which were
mostly grade 1/2.
Conclusions: Crizotinib demonstrated a high response rate that was durable, with a
median progression-free survival of 8.1 months. Crizotinib has a favorable tolerability
profile. These findings continue to provide strong evidence for crizotinib as a
standard of care for advanced ALK-positive NSCLC.
Overall population Mature population
Total no. of patients, n 901 261
Response-evaluable patients, n 803 259
Demographics:
Median age, years
Male/female, %
ECOG PS 0/1, %
Annals of Oncology
53
52
43/57
46/54
82
83
Adenocarcinoma, %
92
94
Duration of treatment (weeks), median
(range)
20 (