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Annals of Oncology
months; p = 0.04). When analysis was restricted to 24 months follow-up, the
Q-TWiST advantage was smaller but still significant (14.0 versus 13.0 months; 1.0
additional quality-adjusted month; p = 0.04).
Conclusions: This Q-TWiST analysis showed that in patients with previously
untreated WT KRAS mCRC, panitumumab plus FOLFOX significantly improved the
duration of the quality-adjusted survival compared with FOLFOX alone.
Disclosure: J. Wang: The study was funded by Amgen Inc. Z. Zhao: Employed and
stock owner of Amgen Inc. B. Barber: Employed and stock owner of Amgen Inc. J.
Zhang: The study was funded by Amgen Inc. B. Sherrill: The study was funded by
Amgen Inc. S. Braun: Employed and stock owner of Amgen Inc. R. Sidhu: Employed
and stock owner of Amgen Inc. M. Gallagher: Employed and stock owner of Amgen
Inc. J. Douillard: The study was funded by Amgen Inc.
565P BEVACIZUMAB (BEV) + CHEMOTHERAPY (CT) BEYOND FIRST
PROGRESSION IN PATIENTS (PTS) WITH METASTATIC
COLORECTAL CANCER (MCRC) PREVIOUSLY TREATED WITH
BEV-BASED THERAPY: OVERALL SURVIVAL SUBGROUP
FINDINGS FROM ML18147
J.M. Vieitez de Prado 1 , C. Borg 2 , D. Arnold 3 , R. Greil 4 , E.J.D. Van Cutsem 5 ,
R. von Moos 6 , J. Bennouna 7 , I. Reyes-Rivera 8 , B. Bendahmane 9 , S. Kubicka 10
1 Medical Oncology, Hospital Central de Asturias (HUCA), Oviedo, SPAIN,
2 Medical Oncology, University Hospital Besançon, Besançon, FRANCE,
3 Medical Oncology, Hubertus Wald Tumor Center, University Cancer Center
Hamburg (UCCH), Hamburg, GERMANY, 4 Oncology Centre, III Medizinische
Universitätsklinik Salzburg, Salzburg, AUSTRIA, 5 Digestive Oncology, University
Hospital Gasthuisberg, Leuven, BELGIUM, 6 Medical Oncology, Kantonal
Hospital Graubünden, Chur, SWITZERLAND, 7 Medical Oncology, Institut de
Cancérologie de l’Ouest, Nantes, FRANCE, 8 Statistics, Genentech Inc., South
San Francisco,CA, UNITED STATES OF AMERICA, 9 GPS Oncology,
F. Hoffmann-La Roche, Basel, SWITZERLAND, 10 Internal Medicine, Cancer
Center Reutlingen, Reutlingen, GERMANY
Background: ML18147 evaluated the benefit of continuing BEV + standard CT as
second-line (2L) treatment for pts with mCRC progressing after first-line (1L)
BEV-containing therapy. Here we report results of pre-specified subgroup and
exploratory KRAS mutation analyses.
Methods: Pts with unresectable, histologically confirmed mCRC progressing within 3
mo after discontinuing 1L BEV were randomised to 2L fluoropyrimidine + oxaliplatin
or irinotecan (crossed over from 1L) ± BEV (2.5 mg/kg/wk equivalent). The primary
endpoint was overall survival (OS). Subgroup analyses for OS were performed using
the same statistical method as for the primary analysis.
Results: 409 pts were randomised to BEV + CT and 411 to CT (1 pt not treated).
Median OS was 11.2 mo for BEV + CT vs 9.8 mo for CT (unstratified HR = 0.81;
95% CI 0.69–0.94; p = 0.0062). Subgroup analyses for OS were generally consistent
with the overall population (Table). While the treatment effect in female pts
appeared to be lower, the treatment-gender interaction test was not statistically
significant.
Category Subgroup N HR for OS 95% CI
All All 819 0.81 0.69–0.94
Gender Female
294 0.99 0.77–1.28
Male
525 0.73 0.60–0.88
Age 9mo 369 0.73 0.58–0.92
First-line chemotherapy Oxaliplatin-based 343 0.79 0.62–1.00
Irinotecan-based 476 0.82 0.67–1.00
Time from last BEV dose ≤42 d
630 0.82 0.69–0.97
>42d 189 0.76 0.55–1.06
Liver metastases only No
592 0.81 0.67–0.97
Yes
226 0.79 0.59–1.05
No. of organs with metastasis 1
307 0.83 0.64–1.08
>1
511 0.77 0.64–0.94
KRAS mutation data were available from an exploratory analysis in 616 pts (75%);
median OS for KRAS wild-type (WT) pts was 15.4 mo for BEV + CT vs 11.1 mo
for CT (HR = 0.69, 95% CI 0.53–0.90; p = 0.0052); in KRAS mutant (MT) pts
median OS was 10.4 vs 10.0 mo, respectively (HR = 0.92; 95% CI 0.71–1.18; p =
0.4969). Median PFS for KRAS WT pts was 6.4 mo for BEV + CT vs 4.5 mo for
CT (HR = 0.61; 95% CI 0.49–0.77; p < 0.0001); in KRAS MT pts median PFS was
5.5 vs 4.1 mo, respectively (HR = 0.70; 95% CI 0.56–0.89; p = 0.0027). No
treatment interaction by KRAS status was seen for OS (p = 0.1266) or PFS (p =
0.4436).
Conclusions: ML18147 showed that BEV + CT continued beyond progression
significantly improves survival vs CT alone. Findings from the subgroup analyses for
OS were generally consistent with the overall population.
Disclosure: J.M. Vieitez de Prado: Involved in corporate-sponsored trials for Roche.
D. Arnold: Consultant / Advisory Board: Roche. Honoraria: Roche. Research
funding: Roche. R. Greil: Honoraria: Roche Research support: Roche. E.J.D. Van
Cutsem: Research funding: Roche. R. von Moos: Consultant/advisory board: Roche.
Honoraria: Roche. Research funding: Roche. J. Bennouna: Consultant / advisory
board: Roche. Honoraria: Roche. I. Reyes-Rivera: Employed by Genentech Inc. B.
Bendahmane: Employed by F. Hoffmann-La Roche. S. Kubicka: Consultant /
advisory board: Roche. Honoraria: Roche. All other authors have declared no
conflicts of interest.
566P RANDOMIZED PHASE II STUDY OF OXALIPLATIN AND S-1
(OS) VERSUS OXALIPLATIN AND CAPECITABINE (XELOX) IN
PATIENTS WITH METASTATIC OR RECURRENT COLORECTAL
CANCER
D.Y. Zang 1 , I.J. Chung 2 ,H.Oh 3 , K.U. Park 4 , K.H. Lee 5 , B. Han 1 , D.R. Choi 1 ,H.
S. Kim 1 , J.H. Kim 1
1 Internal Medicine, Hallym University Medical Center Hallym University College of
Medicine, Anyang, KOREA, 2 Medical Oncology, Chonnam National University
Hwasun Hospital, Jeollanamdo, KOREA, 3 Internal Medicine, Gangneung Asan
Hospital, Gangneung, KOREA, 4 Internal Medicine, Dongsan Medical Center,
Keimyung University, Daegu, KOREA, 5 Internal Medicine, Yeungnam University
Hospital, Daegu, KOREA
Background: Combination oxaliplatin and S-1 (OS) or oxaliplatin and capecitabine
(XELOX) chemotherapy have shown significant efficacy in advanced colorectal
cancer. To evaluate those efficacy and safety, we performed a randomized phase II
study in patients with metastatic or recurrent colorectal cancer.
Methods: Eligible patients were those who had measurable lesions and had no
previous history of chemotherapy except adjuvant chemotherapy. Eight-eight patients
were randomly assigned to receive oxaliplatin 130 mg/m 2 was administered
intravenously on day 1 and S-1 80 mg/m 2 (OS, arm A) or capecitabine 2,000 mg/m 2
(XELOX, arm B) was administered orally on days 1-14. Cycles were repeated every
21 days. Patients were treated until proved to have disease progression or
unacceptable toxicity. The primary endpoint of the study was to assess the overall
response rate (ORR).
Results: Characteristics of the patients were well-balanced between arms, except for
primary disease site, where the percentage of colon, rectosigmoid, and rectum were
42%, 16%, and 42% (arm A) and 58%, 22%, and 20% (arm B), and number of
metastatic organs, where the percentage of less than 1 and more than 2 were 53%
and 47% (arm A) and 67% and 33% (arm B). A total of 284 cycles (median 6, range
1-39) in Arm A; 298 cycles (median 5, range 1-19) in arm B were administered.
Eighty-three (41 for arm A and 42 for arm B) patients were evaluated for toxicity
and response. The main toxicities were thrombocytopenia [grade 1/2/3/4 = 8/10/7/1
patients (A); 10/10/7/5 (B)], neutropenia [grade 1/2/3/4 = 9/8/1/0 (A); 8/12/5/2 (B)],
anemia [grade 1/2/3/4 = 21/13/3/1 (A); 20/11/4/0 (B)], peripheral neuropathy [grade
1/2/3 = 11/10/0 (A); 11/8/3 (B)], and hand-foot syndrome [grade 1/2/3 = 2/0/0 (A);
7/1/2 (B)]. There were 3 CR, 11 PR, 25 SD and 2 PD (A); 5 CR, 13 PR, 16 SD and 7
PD (B). The confirmed ORR in the intention-to-treat population was 32.6% (95% CI:
18.6-47.4%) in arm A and 40.0% (95% CI, 25.0-55.0%) in arm B. The median time
to progression was 6.7 (95% CI, 4.8-8.7) months (A) and 8.0 (95% CI, 6.3-9.6)
months (B). The median survival time was 19.0 (95% CI, 7.6-30.5) months (A) and
22.1 (95% CI, 17.9-26.3) months (B).
Conclusion: These data suggest that both OS and XELOX regimens are active and
are well tolerated regimens in patients with metastatic or recurrent colorectal cancer.
Disclosure: All authors have declared no conflicts of interest.
567P NEOADJUVANT MULTIDISCIPLINARY PHASE II STUDY
(BRANCH) OF AN EARLY BEVACIZUMAB SCHEDULE PLUS
CHEMO-RADIATION THERAPY IN RECTAL CANCER:
EFFICACY, SAFETY, AND BIOMARKERS
A. Avallone, E. Di Gennaro, L. Aloj, P. Delrio, B. Pecori, F. Tatangelo, A. Petrillo,
V.R. Iaffaioli, S. Lastoria, A. Budillon
Gastrointestinal Oncology, National Cancer Institute of Naples, Fondazione G.
Pascale, Naples, ITALY
Background: In BRANCH study we assess the safety and efficacy of an experimental
schedule of early (4 days before) bevacizumab (BEV) added to neoadjuvant
chemotherapy (CT) and radiotherapy (RT) in poor-risk locally advanced rectal
cancer (pLARC) patients (pts) and explore the potential of circulating endothelial
cells (CECs) and tumor lesion glycolysis (TLG) as surrogate markers of pathological
response(PR).
Patients and methods: 46 pts (cT4, cN + , cT3≤ 5 cm from the anal verge and/or
positive circumferential margin, M1 resectable) received 3 biweekly courses of
Volume 23 | Supplement 9 | September 2012 doi:10.1093/annonc/mds397 | ix193