Berenson, K

Chouaid, C

Sherman, S

Vergnenegre, A

Walzer, S

Elsevier - Publisher Connector 

13th Euro Abstracts A255
PCN21
FIRST-LINE BEVACIZUMAB-BASED THERAPY VERSUS PEMETREXED + 
CISPLATIN FOR THE TREATMENT OF ADVANCED ADENOCARCINOMA 
NONSQUAMOUS NON-SMALL CELL LUNG CANCER: INDIRECT 
COMPARISON APPLYING REAL-LIFE OUTCOMES
Berenson K1, Chouaid C2, Vergnenegre A3, Sherman S1, Walzer S4
1Analytica International Inc., New York, NY, USA; 2Hôpital St Antoine, Paris, France; 3SIME, 
Limoges, France; 4F. Hoffmann-La Roche Pharmaceuticals, Basel, Switzerland
OBJECTIVES: In the absence of head-to-head clinical trial data, an indirect compari-
son of bevacizumab (BEV) versus pemetrexed (PMX) was conducted to compare 
survival outcomes among adenocarcinoma nonsquamous metastatic Non-Small Cell 
Lung Cancer (mNSCLC) patients. METHODS: An adjusted matched indirect analysis 
was conducted to estimate overall survival (OS) in adenocarcinoma mNSCLC patients 
treated with BEV + cisplatin doublet therapy using patient-level data from SAiL 
(ECCO/ESMO 2009). These estimates were indirectly compared to previously pub-
lished survival outcomes for PMX + cisplatin-treated patients (Oncologist 
2009;14:253–263) by calculating the median ratio (MR) for OS. a subset of the SAiL 
population was selected to more closely approximate the PMX population by exclud-
ing patients who did not have cisplatin doublet as their baseline treatment, those with 
a baseline Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 
> = 2, and those with non-adenocarcinoma histology. This sample of BEV patients 
was matched to the adenocarcinoma subgroup from the PMX trial on stage of disease 
and ECOG PS. One thousand repeated random matched samples of the SAiL data 
were produced to generate a distribution of survival outcomes and infer a 95% con-
ﬁ dence interval (CI) around the mean of all sampled median survival estimates. 
RESULTS: After adjusted matching, the estimated median OS beneﬁ t for BEV patients 
was 15.6 months (95% CI: 15.0, 16.5) compared to the published median OS of 12.6 
months (95% CI: 10.7, 13.6) for PMX patients. BEV patients had longer median OS 
with an MR of 0.81 (95% CI: 0.71, 0.82). CONCLUSIONS: Results from this indirect 
comparison show that BEV-based therapy provides superior overall survival outcomes 
when compared to PMX in adenocarcinoma mNSCLC patients.
PCN22
EFFICACY AND CARDIAC SAFETY OF TRASTUZUMAB (T) IN THE 
ADJUVANT TREATMENT OF HER2-POSITIVE EARLY-STAGE BREAST 
CANCER: A SYSTEMATIC REVIEW (SR) AND META-ANALYSIS (MA)
Botrel TEA, Clark O, Clark LGO, Paladini L, Faleiros E, Pegoretti B
MedInsight-Evidências, Campinas, Brazil
OBJECTIVES: Trastuzumab (T) is now part of the standard adjuvant treatment for 
HER2 positive, breast cancer patients. However, the results of the studies are not 
uniform and there are still doubts about the ideal indication and schedule for its use. 
Our objective was to perform a systematic review (SR) and meta-analysis (MA) of all 
randomized controlled trials (RCT) comparing efﬁ cacy of Chemotherapy (CHEM) 
plus T versus CHEM plus observation in the adjuvant treatment of HER2-positive 
early-stage breast cancer. METHODS: Several databases were searched, including 
MEDLINE, EMBASE, LILACS, and CENTRAL. The primary end points were pro-
gression-free survival (PFS) and overall survival (OS). a subgroup analysis was per-
formed to evaluate the inﬂ uence of the use of T concurrent or sequential to CHEM. 
RESULTS: Overall, 730 references were identiﬁ ed and screened. The ﬁ nal analysis 
included six trials comprising 13,940 patients. The PFS was higher in the group of 
patients treated with CHEM plus T (ﬁ xed effect: HR = 0.61, CI 95% = 0.56 to 0.66; 
P < 0.00001) with signiﬁ cant heterogeneity (χ2 = 13,33 df = 5 (P = 0.02); I2 = 62%). 
This result remained favorable to the use of T after the random-effects model analysis 
was performed (HR = 0.63, CI 95% = 0.54 to 0.73; P < 0.00001). OS was better for 
patients who received T (ﬁ xed effect: HR = 0.71, CI 95% = 0.62 to 0.81; P < 0.00001 
and random-effects: HR = 0.71, CI 95% = 0.60 to 0.84; P < 0.0001) with moderate-
level heterogeneity (χ2 = 7,12 df = 5 (P = 0.21); I2 = 30%). There was a signiﬁ cant 
interaction between the concurrent and sequential use of T and CHEM, suggesting 
that the concurrent use may be more effective. CONCLUSIONS: Trastuzumab 
increased progression-free survival and overall survival of patients especially when 
administered concomitantly to chemotherapy.
PCN23
SIMULATION AND COMPARISON OF PROGRESSION-FREE-SURVIVAL 
OUTCOMES OF SEQUENTIAL TARGETED THERAPY IN METASTATIC 
RENAL-CELL CARCINOMA
Mickisch GH1, Schwander B2, Cassinello JG3, Carles J4, Walzer S5, Nuijten M6
1Center of Operative Urology Bremen, Bremen, Germany; 2AiM GmbH—Assessment in 
Medicine, Research and Consulting, Lörrach, Germany; 3University Hospital Guadalajara, 
Guadalajara, Spain; 4Vall d’Hebron University Hospital, Barcelona, Spain; 5F. Hoffmann-La 
Roche Pharmaceuticals AG, Basel, Switzerland; 6Ars Accessus Medica, Jisp, The Netherlands
OBJECTIVES: The novel targeted agents bevacizumab (BEV), sorafenib (SOR), suni-
tinib (SUN), everolimus (EVR), and pazopanib (PAZ) have each demonstrated activity 
in metastatic renal-cell carcinoma patients. One of the remaining key questions is 
which therapy sequence provides the most valuable outcome in terms of progression-
free-survival (PFS). METHODS: A Markov disease model was developed using pivotal 
trial evidence. All patients were assumed to be treatment-naïve, with a good or inter-
mediate prognosis, and to enter the model in “PFS,” receiving ﬁ rst-line treatment with 
either BEV + interferon-alpha-2a (IFN), SUN, PAZ, or IFN alone, taking into account 
current EMA licenses (e.g., BEV + IFN indicated only for ﬁ rst-line therapy). After 
initial treatment, patients were assumed to either die, progress to a subsequent line of 
therapy, or remain in PFS. Hence, in case of p. RESULTS: The most valuable therapy 
sequence in terms of total PFS was BEV + IFN → PAZ → SUN → SOR → EVR 
resulting in a mean PFS time of 33.2 months (95% conﬁ dence interval [CI]: 31.3–
35.2). The sequence BEV + IFN → PAZ → SOR → SUN → EVR obtained comparable 
results (mean PFS 33.2; 95% CI: 31.3–35.1). The ﬁ rst-line PAZ sequences PAZ → 
SUN → SOR → EVR (mean PFS 28.6; 95% CI 26.6–31.2) and PAZ → SOR → SUN 
→ EVR (mean PFS 28.6; 95%CI 26.6–31.2) were the second-best alternatives, fol-
lowed by the most valuable IFN ﬁ rst-line sequence (IFN → PAZ → SUN → SOR → 
EVR; mean PFS 28.5; 95% CI 26.8–30.4) and the most valuable SUN ﬁ rst-line 
sequence (SUN → PAZ → SOR → EVR; mean PFS 26.7; 95% CI 24.4–29.1). The 
incremental PFS difference between the best therapy sequences (ﬁ rst-line BEV + IFN; 
mean PFS 33.2 months) and the second-best therapy sequences (PAZ ﬁ rst-line; mean 
PFS 28.6 months) of 4.6 months reached statistical signiﬁ cance (P < 0.004 for each 
possible comparison). Additional overall survival simulations have conﬁ rmed these 
ﬁ ndings. CONCLUSIONS: Modeling simulation indicates that patients’ PFS outcomes 
could be improved signiﬁ cantly, if therapy started with ﬁ rst-line BEV + IFN compared 
to other ﬁ rst-line agents (PAZ, SUN, or IFN alone).
PCN24
EFFICACY OF ADJUVANT CHEMOTHERAPY WITH GEMCITABINE 
(GEM) COMPARED TO SURGERY-ONLY IN PATIENTS WITH RESECTED 
PANCREATIC CANCER: SYSTEMATIC REVIEW (SR) AND META-
ANALYSIS (MA)
Botrel TEA, Clark O, Clark LGO, Paladini L, Faleiros E, Pegoretti B
MedInsight-Evidências, Campinas, Brazil
OBJECTIVES: We aimed to perform a systematic review (SR) with meta-analysis 
(MA) of all randomized controlled trials (RCT) comparing the efﬁ cacy of adjuvant 
chemotherapy with gemcitabine (GEM) versus observation in patients with resected 
pancreatic cancer. METHODS: Several databases were searched, including MEDLINE, 
EMBASE, LILACS, and CENTRAL. The primary end points were progression-free 
survival (PFS) and overall survival (OS). The data extracted from the studies were 
combined by using hazard ratio (HR) with their corresponding conﬁ dence intervals 
of 95% (CI 95%). RESULTS: Overall, 233 references were identiﬁ ed and screened. 
The ﬁ nal analysis included two trials comprising 472 patients evaluated. The propor-
tion of patients that underwent surgery with curative intent (R0 or R1 resection) was 
similar between the studies as well as their ages and nodal status. The progression-free 
survival was higher in the group of patients who were treated with adjuvant chemo-
therapy including GEM (ﬁ xed effect: HR = 0.59, CI 95% = 0.50 to 0.70; P < 0.00001) 
and no heterogeneity was found (χ2 = 0.01, df = 1 (P = 0.94); I2 = 0%). Overall survival 
was also higher in patients treated with GEM (ﬁ xed effect: HR = 0.81, CI 95% = 0.67 
to 0.98; P = 0.03) yet again no heterogeneity was detected (χ2 = 0.07, df = 1 [P = 
0.79]; I2 = 0%). CONCLUSIONS: Adjuvant chemotherapy with gemcitabine increased 
progression-free survival and overall survival of patients with resected pancreatic 
cancer.
PCN25
DID THE UPTAKE OF NEW TREATMENT OPTIONS CHANGE THE 
TREATMENT STRATEGY IN PATIENTS WITH COLORECTAL CANCER 
AND PRIMARY NONRESECTABLE METASTASES? THE RESULTS OF 
LARGE POPULATION-BASED SURVEY IN GERMANY 2006–2007
Kellermann L1, Arnold D2
1Oncology InformationService, Freiburg, Germany; 2Hematology & Oncology, Martin Luther 
University Halle-Wittenberg, Halle/Saale, Germany
OBJECTIVES: The survey was initiated to gain insights into the changes of treatment 
patterns in treatment of metastatic colorectal cancer and the implementation of the 
results of clinical trials in daily practice. METHODS: A representative sample of 
centers (82) was selected with regard to the distribution of treated prevalence in 
colorectal cancer in institutions (university hospitals, community hospitals, ofﬁ ce-
based oncologists) and regional population density. The physicians reported all pts. 
with a treatment decision in colorectal cancer in the respective reporting period May 
2006 to April 2007. The database contains 3254 pts. with a retrospective record of 
their entire treatment history. The treatment patterns were analyzed in the whole 
patient group and in subgroups according to resectability of metastases, the treatment 
objectives (especially secondary resectability of metastases), used systemic treatment 
regimen, age, concomitant diseases, and performing institution type. The statistics 
were performed in SPSS by bivariate analyses with two-sided chi-square test. In the 
next step, the decisive parameters for treatment choice were deﬁ ned by logistic regres-
sion in multivariate analysis. RESULTS: The clinical trial data were taken up very 
soon in clinical reality. The correlation of drug efﬁ cacy and resectability of metastases 
was transferred into the disease management of colorectal cancer. The patient share 
with treatment objective “secondary resection of metastases” increased signiﬁ cantly 
(18% 2004 vs. 27% 2006–2007, P = 0.000%). In this subgroup, the patient share 
treated with targeted therapy was signiﬁ cantly higher than in patients with other 
treatment objectives (34% vs. 19%, P = 0.000%). CONCLUSIONS: The method used 
for creation of the database and for the statistic analyses has been proven as appropri-
ate for the objectives of this survey. The resectability of metastases is recognized as 
an important treatment objective. Therefore, targeted therapy was implemented more 
frequently in treatment regiments for patients deemed secondary resectable, compared 
to other treatment aims.


PCN21 FIRST-LINE BEVACIZUMAB-BASED THERAPY VERSUS PEMETREXED + CISPLATIN FOR THE TREATMENT OF ADVANCED ADENOCARCINOMA NONSQUAMOUS NON-SMALL CELL LUNG CANCER: INDIRECT COMPARISON APPLYING REAL-LIFE OUTCOMES 

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PCN21 FIRST-LINE BEVACIZUMAB-BASED THERAPY VERSUS PEMETREXED + CISPLATIN FOR THE TREATMENT OF ADVANCED ADENOCARCINOMA NONSQUAMOUS NON-SMALL CELL LUNG CANCER: INDIRECT COMPARISON APPLYING REAL-LIFE OUTCOMES

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