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

TPS4140 General Poster Session (Board #53C), Mon, 8:00 AM-12:00 PM
Lapatinib in combination with ECF/x in EGFR1 positive first-line metastatic
gastric cancer (GC): A phase II randomized placebo controlled trial (EORTC
40071). Presenting Author: Markus Hermann Moehler, University of
Mainz, Mainz, Germany
Background: Survival of HER2� metastatic GC is prolonged by trastuzumab
when administered with CF/X (VanCutsem, ASCO 2009). Lapatinib inhibits
both EGFR1 and HER2, is active in HER2� GC lines, and has shown
clinical activity in uncontrolled phase II GC trials. A phase III trial of
lapatinib with X � oxaliplatin in HER2� (FISH) GC is closed to recruitment.
Additional unaddressed questions include the efficacy and safety of
lapatinib with ECF/X (epirubicin � cisplatin � 5-FU or capecitabine (X),
which is a preferred chemotherapy (CT) regimen in GC), and its activity in
patients (pts) with discordant FISH or IHC HER2 status or EGFR1�.
Methods: This is a phase II, randomized, double- blind, placebo controlled,
multicenter trial sponsored by the EORTC. About 480 pts with adenocarcinoma
of the stomach or esophagogastric junction not amenable to curative
surgery and without prior palliative CT are screened centrally for HER2/
EGFR1 by FISH and IHC. Patients are enrolled into one of two strata: 1)
HER2 FISH- and IHC 2/3�, or 2) HER2 IHC 0/� and EGFR1 FISH� or IHC
2/3�. Pts HER2 FISH�/IHC 2/3� and pts without HER2/EGFR1 by
FISH/IHC will be excluded. 168 pts are anticipated to be randomized to
lapatinib 1,250 mg cont. until progression or placebo, administered 6
cycles of ECF or ECX (72/96 in stratum 1/2, respectively).The primary
endpoint is progression-free survival (PFS) in stratum 2 and 77 events are
needed for 80% power to detect an increase in PFS from 4 to 6.5 months
with lapatinib (HR�0.615, one-sided alpha 10%). Secondary endpoints
include PFS, toxicity, response rate, overall survival, and correlation of
HER2/EGFR1 status with response. Currently, half of all screened patients
(19/38) have been randomized. So far, 8/38 (21%) pts were HER2�
according TOGA criteria. By FISH or IHC, 14/38 were EGFR1�, with 4/14
pts double HER2/EGFR�. Enrolment continues in 5 centers with about
4-10 patients per month. A safety cohort analysis will be performed in the
first 15 pts receiving lapatinib. Conclusions: This is the first trial to analyze
prospectively and separately the role of lapatinib combined with chemotherapy
in EGFR1� GC pts stratified by FISH/ IHC.
TPS4142 General Poster Session (Board #53E), Mon, 8:00 AM-12:00 PM
Postoperation chemotherapy with S1 and docetaxel in curatively resected
gastric cancer of stage III (POST trial). Presenting Author: Minkyu Jung,
Gachon University Gil Hospital, Incheon, South Korea
Background: Complete surgical resections remains the only chance for cure
in patients with gastric cancer, but approximately from 40% to 80% of
patients still have recurrences and most patients ultimately die from their
disease. The recent adjuvant trials in gastric cancer showed significantly
improved survival in patients with adjuvant chemotherapy than those with
surgery alone. However, further studies need for the effect of adjuvant
chemotherapy following D2 dissected gastric cancer patients, especially in
advanced gastric cancer. S-1 is an oral anticancer drug, a prodrug of
fluorouracil, very effective in gastric cancer. Docetaxel is the first drug that
showed survival benefits when added to the two drugs in advanced gastric
cancer patients. And docetaxel is also synergistic anti-cancer effect with
S-1 in advanced gastric cancer. Base on this background, the aim of this
study is to detect a significant increase in 3 –year disease free survival
(DFS) of adjuvant chemotherapy with docetaxel and S-1(DS) relative to
those with S-1 and cisplatin (SP) in patients with stage III gastric cancer
Methods: This study is an open-label, phase 3, randomized controlled trial,
multicenter in South Korea. Patients with stage III (AJCC 7th edition)
gastric cancer who had had curative D2 gastrectomy is randomly assigned
to receive adjuvant chemotherapy of eight 3-week cycles of intravenous
docetaxel (35 mg/m2 on day 1 and 8 of each cycle) plus oral S-1 (35 mg/m2 twice daily on days 1 to 14 of each cycle) for 6 months (DS) or
chemotherapy of eight 3-week cycles of oral S1 plus intravenous cisplatin
(60 mg/m2 ). After satisfying the screening criteria, patients have been
randomized to the SD or SP arm in a 1:1 ratio. The randomization is
stratified by institution and stage of disease (IIIA vs. IIIB vs. IIIC). The each
stratum has been randomized by using the method of randomly permuted
block. The primary endpoint is 3 year DFS, will analyze by intention to treat.
A total of 290 patients will be enrolled, 67 patients have been treated to
day, with continuing accrual. The trial is registered at ClinicalTrials.gov
(NCT01283217).
Gastrointestinal (Noncolorectal) Cancer
273s
TPS4141 General Poster Session (Board #53D), Mon, 8:00 AM-12:00 PM
TOPGEAR: An international randomized phase III trial of preoperative
chemoradiotherapy versus preoperative chemotherapy for resectable gastric
cancer (AGITG/TROG/EORTC/NCIC CTG). Presenting Author: Trevor
Leong, Peter MacCallum Cancer Centre, Melbourne, Australia
Background: Optimal management of patients with resectable gastric
cancer remains unknown. Since the INT0116 and MAGIC trials, there are 2
standards of care for adjuvant therapy: postoperative chemoradiotherapy
(CRT) and perioperative ECF chemotherapy. The important question arising
from these studies is whether CRT is superior to chemotherapy alone as
adjuvant therapy. This randomized phase II/III trial will compare CRT to
chemotherapy alone in the preoperative setting. Methods: Patients with
resectable adenocarcinoma of the stomach or gastroesophageal junction
will be randomized to receive either preoperative chemotherapy alone
(ECFx3 as per MAGIC regimen) or preoperative CRT (ECFx2 followed by
45Gy of radiation with concurrent 5-FU). Following surgery, both groups
will receive 3 further cycles of ECF. The trial is being conducted in two
Parts; Part I (phase II component) will recruit 120 patients with the aim of
demonstrating sufficient efficacy and safety of preoperative CRT, as well as
trial feasibility. Part II (phase III component) will recruit a further 632
patients to provide a total of 752. The primary endpoint for Part I is
pathological complete response rate, and for Part 2 it is overall survival.
The trial includes formal quality of life and biological sub-studies. In
addition, the trial incorporates a rigorous quality assurance program that
includes real time central review of radiotherapy plans and central review of
surgical technique. Current status: This study is an international, intergroup
trial led by the Australasian Gastro-Intestinal Trials Group (AGITG),
in collaboration with the Trans-Tasman Radiation Oncology Group (TROG),
European Organisation for Research and Treatment of Cancer (EORTC) and
the NCIC Clinical Trials Group. To date, 36 patients have been recruited
from 20 sites in Australia and New Zealand; European and Canadian sites
will commence recruitment in 2012.
TPS4143 General Poster Session (Board #53F), Mon, 8:00 AM-12:00 PM
ST03: A randomized trial of perioperative epirubicin, cisplatin plus
capecitabine (ECX) with or without bevacizumab (B) in patients (pts) with
operable gastric, oesophagogastric junction (OGJ) or lower oesophageal
adenocarcinoma. Presenting Author: Elizabeth C Smyth, The Royal Marsden
Hospital, Sutton, United Kingdom
Background: Perioperative ECX chemotherapy is a standard of care for
localised gastric/OGJ/lower oesophageal adenocarcinoma (Cunningham
NEJM 2006). B is a monoclonal antibody targeting VEGF-A, and in
combination with chemotherapy results in improved response rates (RR)
and progression free survival in advanced gastric cancer (Ohtsu JCO 2011).
The aim of ST03 is to assess the safety and feasibility (stage I, first 200 pts)
and efficacy (stage II) of the addition of B to perioperative ECX chemotherapy.
Methods: ST03 is a multicentre, open-label, phase II/III randomised
trial ongoing at 92 UK centres; sites in Germany will open in
2012. Eligibility criteria are histologically proven, untreated, resectable,
lower oesophageal, OGJ or gastric adenocarcinoma; age �18 years; WHO
PS 0-1; and adequate cardiac ejection fraction (EF). Exclusion criteria are
TIA/CVA or MI �1 year; uncontrolled hypertension; �Grade II NYHA heart
failure; recent gastrointestinal inflammatory conditions or major surgery/
trauma/open biopsy �28d of study entry. Pts receive 3 pre- and 3
postoperative ECX (epirubicin 50 mg/m2 iv D1, cisplatin 60 mg/m2 iv D1
and capecitabine 1250mg/m2 /D1-21) �/- B 7.5mg/kg D1 q3wk during
chemotherapy, then 6 Bev q3wk (investigational arm). Surgery is prespecified
and laparoscopic procedures allowed only after quality assurance
review. All specimens undergo central pathology review; blood and tissue
collection for translational correlates is ongoing. The primary outcome
measures for Stage I (safety results including cardiac EF) have been
reported (Okines ASCO 2011). The stage II primary outcome measure is
overall survival. Secondary outcome measures are RR, resection rate,
disease free survival, toxicity, and QoL. An MRI substudy is open, a PET
substudy is planned. 558 of ~950 pts required have been recruited,
accrual expected to complete in 2013. An embedded pilot study within
ST03 randomising HER2 positive patients to ECX � lapatanib will open in
2012. Trial sponsored and co-ordinated by the MRC Clinical Trials Unit and
funded by Cancer Research UK (CRUK06/025, NCT00450203).
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