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

7603 General Poster Session (Board #52E), Sat, 1:15 PM-5:15 PM
MIMEB: A phase II trial to evaluate FDG-PET/FLT-PET and DCE-MRI for
early prediction of efficacy in patients with advanced non-small cell lung
cancer treated with erlotinib and bevacizumab. Presenting Author: Matthias
Scheffler, Lung Cancer Group Cologne, Department I of Internal
Medicine and Center for Integrated Oncology, University Hospital Cologne,
Cologne, Germany
Background: Since the introduction of targeted therapy into the treatment of
NSCLC, molecular imaging tools gain in importance for assessment of
pharmacodynamics, pharmacokinetics and prediction of therapeutic outcome.
Tumor metabolism (by FDG-PET), proliferation (by FLT-PET), and
vascularization (by DCE-MRI) can be noninvasively assessed to quantify the
effects of targeted therapy on tumor biology. We set up a trial to evaluate
the effects of combined erlotinib (E) and bevacizumab (B) treatment in
patients with advanced non-squamous cell NSCLC and to identify prospectively
patients who benefit from this combination. Methods: Patients with
non-squamous NSCLC stage IV without prior systemic therapy received at
least six weeks of combined E and B. FLT and FDG-PET scans as well as
DCE-MRI-scans were performed at baseline, after 1 week of therapy and
after 6 weeks of therapy. Standard uptake values of the PET scans and
vascularization parameters of the DCE-MRI scans were analyzed and
coregistrated. Tumor specimens were analysed within a network screening
panel. The primary objective of this trial was to evaluate the accuracy of the
imaging tools for early prediction of nonprogression and PFS and its
association with molecular markers. Results: Of the 40 patients, all
received FDG-PET analyses, whereas FLT-PET was performed in 38
patients and DCE-MRI in 36 patients. Median OS was 13.4 months,
median PFS was 5.9 months. Until January 2012, tissue specimens from
25 patients have been genetically analysed. First results show that even
patients with KRAS, PI3K and BRAF mutations profiting from the combination
either by response or prolonged PFS could be identified by early
imaging assessment. Conclusions: The efficacy of E �B in unselected
patients with NSCLC was comparable with platinum-based chemotherapy.
In order to identify imaging-based predictive biomarkers to identify the
subpopulation of patients with pronounced benefit of this combination
FDG-, FLT- PET and DCE–MRI were successfully implemented in the
treatment plan. Results of the imaging analysis and the correlation with
tissue-based biomarkers will be presented.
7605 General Poster Session (Board #52G), Sat, 1:15 PM-5:15 PM
Impact of disease progression (DP) date determination method on post
progression survival (PPS) and DP metrics in advanced lung cancer.
Presenting Author: Sumithra J. Mandrekar, Mayo Clinic and NCCTG,
Rochester, MN
Background: Overall survival (OS) can be partitioned into progression-free
survival (PFS) and PPS. PPS helps to understand trial results, especially
when PFS and OS data on trial treatment effects are discordant. At ASCO
2011, we reported that the magnitude of difference in the PFS estimates
using different DP date methods was large enough to alter trial conclusions.
Here, we investigate the impact of the DP date method on 1) PPS
estimates, and 2) predictive utility of DP metrics on subsequent OS (SOS).
Methods: Individual patient (pt) data from 14 trials were pooled. DP date
was determined using: reported progression date (RPD) (method 1, M1),
one day after last progression-free (PF) scan (M2), and midpoint between
last PF scan and RPD (M3). PPS was estimated using the method of
Kaplan-Meier for the 3 DP date methods. A flexible landmark analysis at 2,
4, and 6 months (mos) using Cox proportional hazards model was used to
assess the impact of DP status (progression versus no-progression) on SOS
(using M1, M2, or M3). Results: Among NSCLC (SCLC), 87% (91%) of pts
reported DP. As expected, the PPS estimates were the lowest for RPD,
highest for M2, and in-between for M3 (a direct consequence of the DP
date method); with no difference by arm for the randomized trials.
Regardless of the DP date method, patients who were progression-free had
improved SOS (NSCLC: Hazard ratio, HR��0.33; p � 0.0001; SCLC:
HR��0.48; p � 0.002) at each landmark time point, with comparable
concordance index (SCLC: 0.57-0.65; NSCLC: 0.63-0.67), i.e., ability to
discriminate patients with different SOS outcomes. Conclusions: While the
DP date methods do not impact the predictive utility of the DP metrics, they
significantly impact PPS estimates. The translation of a significant treatment
effect on PFS to an effect on OS is influenced by PPS (longer PPS
dilutes effect on OS). Standards for declaring DP date are thus critical to
trial design and for trial go/no-go decisions.
Progression date determination
method
NSCLC (10 trials; n�610)
(median OS � 9.6)
Median PFS, and PPS estimates (mos)
SCLC (4 trials; n�114)
(median OS � 8.7)
PFS PPS PFS PPS
Method 1 4.3 3.8 2.8 4.7
Method 2 2.5 5.9 1.2 7.1
Method 3 3.4 4.7 2.0 5.6
Lung Cancer—Non-small Cell Metastatic
505s
7604 General Poster Session (Board #52F), Sat, 1:15 PM-5:15 PM
Meta-analysis of progression-free survival as a predictor of overall survival
in locally advanced or metastatic non-small cell lung cancer trials.
Presenting Author: Evadne Jane Turner, Boehringer Ingelheim Pty Ltd,
Sydney, Australia
Background: Access to new oncology treatments for non-small-cell lung
cancer (NSCLC) could be expedited if progression free survival (PFS) was
accepted by payers as a valid endpoint predictive for overall survival (OS).
We investigated the relationship between PFS and OS in advanced NSCLC,
which has previously been limited by available data. Methods: A systematic
review of the published literature was conducted (1988 to August 2011;
Medline/Embase/Cochrane). Identified studies were assessed against the
following criteria for inclusion in the analysis: randomised design; NSCLC;
advanced disease (Stage IIIb or IV); pharmacological treatment in 2 or more
groups; reported outcomes included median OS and median PFS. For each
pair of treatment groups compared, the median OS difference and the
median PFS difference were calculated. The data were analysed with
locally weighted least squares regression (LOWESS) to validate the linear
relationship. Unweighted and weighted linear regression was used to test
the significance of the relationship between OS difference and PFS
difference. Results: A total of 124 clinical trials, with 40,568 patients,
were included in the analysis. The studies ranged from middle aged cohorts
to the elderly. Median performance status (ECOG/WHO) was 1. 70% of
studies were first line and therapy type was predominantly chemotherapy
(57%). 19 studies (15%) reported use of crossover or rescue therapy.
Weighted linear regression demonstrated a highly significant linear relationship
between OS difference and PFS difference (Table). The results
suggest that a 1 month difference in PFS is associated with approximately
1.3 months difference in OS. Conclusions: Analysis of NSCLC trials showed
the treatment effect on PFS was predictive of the treatment effect on OS.
With increased use of multiple lines of treatment and crossover/rescue
therapy in new NSCLC trials OS differences are frequently confounded,
making PFS an important outcome for health care decision making.
Statistic
Parameter Estimate SE 95% CI t-statistic p value
Intercept -0.260 0.209 (-0.674, 0.154) -1.242 0.214
Slope 1.317 0.160 (1.000, 1.634) 8.226 �0.001
R-squared 36.6%
7606 General Poster Session (Board #52H), Sat, 1:15 PM-5:15 PM
Metastatic NSCLC: Treatment patterns, outcomes, and costs of newer
agents. Presenting Author: Adrian G. Sacher, Division of Medical Oncology
and Hematology, Princess Margaret Hospital, University of Toronto, Toronto,
ON, Canada
Background: New therapies for metastatic NSCLC have improved survival in
clinical trials. The increased cost of these agents has led to variable drug
funding and treatment across jurisdictions. Here we review patterns,
real-world outcomes and costs of metastatic NSCLC treatment in the
province of Ontario. Methods: All patients diagnosed with metastatic
NSCLC from 2005-2009 were identified from the Ontario Cancer Registry
with demographic, histologic and mortality data. Treatment records from
the Ontario New Drug Funding Program and centralized treatment database
were linked. Statistical analysis involved Wilcoxon rank sum, Kruskal-
Wallis, Cochran-Armitage trend and likelihood ratio tests where appropriate.
Results: 8113 metastatic NSCLC patients were identified. The median
age was 68; 39% had adenocarcinoma, 14% squamous carcinoma and
43% histology not otherwise specified. Most were treated in regional cancer
centers (92%). The majority (76%) did not receive systemic therapy; 23%
received first-line chemotherapy, most commonly platinum doublets. More
patients received systemic therapy over time (19% in 2005 v 26% in
2009, p �0.0001). Older patients (p �0.0001) and those with squamous
histology (p �0.0001) were less likely to receive systemic therapy. Center
of diagnosis did not affect the likelihood of treatment (p�0.46). The
median time from diagnosis to death was significantly greater among
patients selected to receive chemotherapy (9.3 v 3.2 months, p �0.0001),
and with cisplatin/gemcitabine compared to other doublets (10.7 v 8.2
months, p�0.004). 31% of treated patients received second-line chemotherapy,
predominantly with docetaxel (52%) or pemetrexed (41%).
Pemetrexed use increased significantly over time (8% in 2005 v 71% in
2009, p�0.0001), as did the mean drug cost of second-line therapy
($5939/patient in 2005 v $10,057 in 2009). A longer median survival was
also seen with pemetrexed in adenocarcinoma (17.9 v 15.2 months for
docetaxel, p �0.02). Conclusions: Most metastatic NSCLC patients do not
undergo systemic treatment. First- and second-line treatment outcomes in
this population-based study were similar to clinical trials, confirming better
outcomes with new agents at greater cost.
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