Annual Meeting Proceedings Part 1 - American Society of Clinical ...

506s Lung Cancer—Non-small Cell Metastatic
7607 General Poster Session (Board #53A), Sat, 1:15 PM-5:15 PM
Does change in health-related quality of life (HRQoL) score predict
survival? Analysis of a lung cancer RCT. Presenting Author: Divine Ewane
Ediebah, European Organisation for Research and Treatment of Cancer
Headquarters, Brussels, Belgium
Background: Over 60 cancer clinical trials have shown that baseline
health-related quality of life (HRQoL) scores are prognostic for patient
survival. Few studies have investigated the added value of change in
HRQoL scores. Our aim was to investigate if change in HRQoL scores from
baseline over time is also associated with survival. Methods: We analyzed
data from an EORTC 3-arm randomized clinical trial (RCT) in advanced
non-small-cell lung cancer (NSCLC) patients, comparing
gemcitabine�cisplatin, versus paclitaxel�gemcitabine, versus standard
arm paclitaxel�cisplatin. HRQoL was measured in 394 patients using the
EORTC QLQ-C30 at baseline and after each chemotherapy cycle. The
prognostic significance of sex, age and WHO performance status (0-1 vs. 2)
and the 15 QLQ-C30 subscales were assessed with Cox proportional hazard
models stratified for treatment (level of significance 0.05). Changes in
HRQoL scores from baseline to each chemotherapy cycle assessment were
categorized as “improved”, “stable” and “worsened” using a threshold of
10 points difference. Due to expected attrition, the analysis was limited to
changes from baseline up to cycle 3. Results: There were 248 patients in
cycle 1, 212 in cycle 2 and 196 in cycle 3. We performed analyses
separately using data at cycle 1, cycle 2, and cycle 3. In all analyses,
HRQoL in various subscales and socio-demographic and clinical variables
(physical functioning (hazard ratio [HR] 0.91, 95% CI 0.85-0.98;
p�0.0103), pain (1.11, 1.05-1.17; p� 0.0004), age (0.98, 0.97-1.00,
p�0.0413) and WHO performance status (1.77, 1.09-2.89; p�0.0218)
at cycle 1; pain (1.11, 1.03-1.20; p�0.0016), age (0.98, 0.96-1.00;
p�0.0217) and sex (0.63, 0.42-0.95; p�0.0081) at cycle 2; and role
functioning (0.93, 0.88-1.00; p�0.0128) and age (0.98, 0.96-1.00;
p�0.0081) at cycle 3) predicted survival; however, change in HRQoL was
only an independent predictor for improvement at cycle 1. Conclusions: Our
findings suggest that change from baseline over time in HRQoL, as
measured on subscales of the EORTC QLQ-C30, contains added prognostic
value for survival independent of baseline HRQoL scores. Further work is
needed to assess the robustness and sensitivity of these findings.
TPS7609 General Poster Session (Board #53C), Sat, 1:15 PM-5:15 PM
Pilot trial of molecular profiling and targeted therapies in advanced thoracic
malignancies: Non-small cell lung cancer, small cell lung cancer and
thymic malignancies (CUSTOM). Presenting Author: Ariel Lopez-Chavez,
Oregon Health & Science University, Portland, OR
Background: For decades, clinical trial design strategies have relied upon
the broad classification of tumors into tumor site and histopathology.
Several lines of evidence have shown that a molecular approach to patient
selection may be better in its capacity to improve patient outcomes.
CUSTOM is an innovative clinical trial that allows for the parallel evaluation
of multiple targeted therapies in molecularly selected patients with
multiple cancer histological subtypes and the prospective evaluation of
multiple molecular biomarkers. Methods: All patients with advanced lung
cancer and thymic malignancies and a good performance status are eligible
independently of previous lines of treatment. The trial begins with tumor
biopsy and molecular profiling using a multi-platform approach to identify
oncogenic alterations in more than 34 genes for treatment allocation (12
genes) and exploratory purposes. Depending upon the specific biomarker
identified, patients are then triaged into 5 experimental arms. Erlotinib for
sensitizing EGFR mutations; AZD6244 for KRAS, NRAS, HRAS and BRAF
mutations; MK2206 for PIK3CA, AKT and PTEN mutations and PIK3CA
amplification; Lapatinib for ERBB2 mutations or amplification; Sunitnib
for KIT mutations and PDGFRA mutations and amplification. Patients not
eligible for the experimental treatment arms are enrolled into a standard
treatment arm. Upon disease progression patients are eligible for repeat
biopsy and molecular profiling in order to identify molecular changes and
mechanisms of resistance. All patients are followed until death. The
primary endpoint is response rate and secondary endpoints include
progression-free survival, duration of response and overall survival. With
three disease types and five experimental drugs, there are 15 possible
treatment arms which will be under active consideration. For each of these,
the study will be conducted as an optimal two-stage phase II trial in order to
rule out an unacceptably low 10% clinical response rate in favor of a
modestly high response rate of 40%. As of January 11, 2012, two hundred
and sixteen patients have been enrolled.
7608 General Poster Session (Board #53B), Sat, 1:15 PM-5:15 PM
Three-year survival in stage IV non-small cell lung cancer (NSCLC): The
importance of metastatic distribution. Presenting Author: Daniel D. Karp,
University of Texas M. D. Anderson Cancer Center, Houston, TX
Background: Although long term survival (LTS) is an important goal of lung
cancer treatment, those with metastatic disease at presentation have a
median of only 8-9 months in most series with a small “tail” on the survival
curve. We analyzed a large cohort of Stage IV pts by performance status
(PS), smoking history, number and sites of disease to assess factors
associated with 36 month survival. Methods: From 2004–2008, 526 newly
diagnosed untreated pts with Stage IV NSCLC received initial treatment at
our institution. Sites of disease were analyzed according to lung, brain,
bone, liver, adrenal, skin, malignant effusion, lymphangitic, bulky pleural
disease, and “other”. No patient had definitive surgery. Results: Overall,
58/526 pts (10.8%) survived 36 months or more. 453 pts died within 36
months. 15 pts alive with follow-up time less than 36 months were removed
from further analysis. Of those, 38/58 (65.5%) had only 1 metastatic site
(p�0.001). 14 (24.1%) had 2 sites, only 6 (10.3%) had 3 or more sites.
Those 19 pts with lung to lung spread were the most common (32.8%) with
LTS – reflecting the M1 status in the new International Staging System.
Only 1 LTS pt had liver mets at diagnosis – a solitary lesion treated with
radiofrequency ablation. 20 pts had PS�0 (0.019) and 29 had PS�1
(NS). PS�2 pts made up 6. 2 pts had PS�3 initially. 1 unknown. Only
6/58 (10.3%) were current smokers, 23 (39.7%) were never-smokers
(p�0.001). Adenocarcinoma made up 65.5%. Conclusions: Progress in
lung cancer survival has been slow. Very few LTS pts have more than 1 site
of metastatic disease at presentation, virtually none with liver disease
(p�0.02). Number of metastatic sites and presence of liver metastases
appear to be important stratification variables for lung cancer clinical trials.
TPS7610 General Poster Session (Board #53D), Sat, 1:15 PM-5:15 PM
TIME: A phase IIb/III randomized, double-blind, placebo-controlled study
comparing first-line therapy with or without TG4010 immunotherapy
product in patients with stage IV non-small cell lung cancer (NSCLC).
Presenting Author: Elisabeth A. Quoix, Strasbourg University Hospital,
Strasbourg, France
Background: TG4010 is an immunotherapy product based on a poxvirus
(MVA) coding for the MUC1 tumor-associated antigen and interleukin-2. A
previous study, TG4010.09, which evaluated the combination of first-line
chemotherapy with and without TG4010 in advanced NSCLC, achieved its
primary endpoint based on 6-month progression-free survival (PFS) and
showed that the pre-treatment level of activated Natural Killer (aNK) cells
may be a potential predictive biomarker for TG4010 efficacy (E. Quoix et
al., Lancet Oncol. 2011;12:1125-33). Methods: TIME is a double-blind
phase IIb/III study comparing the combination of first-line therapy with
TG4010 or placebo in stage IV NSCLC patients, Performance Status (PS) 0
or 1 with a MUC1 expressing tumor by immunohistochemistry. The Phase
IIb part of the study aims at prospectively validating aNK level as a
predictive biomarker with PFS as a primary endpoint, by comparing the two
treatment arms in two subgroups defined according to the level of aNK cells
at baseline (normal or high). Bayesian criteria, derived from the TG4010.09
study results, will be used to confirm that, with a large probability, the true
hazard ratio is �1 in patients with normal level of aNK cells and �1 in
patients with high level of aNK cells. The Phase III part of the study will
then compare, by using a frequentist approach, the two treatment arms
with overall survival as a primary endpoint in the patient population
confirmed to be of interest in the Phase IIb part. The phase III part is
powered to detect a 27% reduction in the hazard rate of death. Phase IIb
and III parts of the study will enroll respectively 206 and 800 patients. A
dynamic minimization procedure will be applied at randomization for
histology, prescription of bevacizumab, type of chemotherapy, PS and
center. If qualifying for, patients will receive maintenance therapy after
chemotherapy according to labeling. The study TIME is open to recruitment
and referenced in ClinicalTrials.gov with the identifier NCT01383148.
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