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

4027 Poster Discussion Session (Board #19), Mon, 1:15 PM-5:15 PM and
4:45 PM-5:45 PM
Multicenter randomized phase II trial of cisplatin, irinotecan plus bevacizumab
(PCA) versus docetaxel, cisplatin, irinotecan plus bevacizumab
(TPCA) in patients (pts) with metastatic esophagogastric cancer (MEGCA).
Presenting Author: Peter C. Enzinger, Dana-Farber Cancer Institute,
Boston, MA
Background: In MEGCA, PCA has a 65% response rate (RR) and 8.3 mos
time to progression (Shah. JCO 2006); TPCA has a 66% RR and 8.9 mos
progression-free survival (PFS) (Enzinger. ESMO 2008 updated). Methods:
Chemo naive pts with MEGCA were stratified: ECOG (0/1 vs. 2) and disease
site (Gastric or GEJ/esophageal) and randomized 1:1 to PCA or TPCA. PCA
-- cisplatin 30mg/m2 and irinotecan 65mg/m2 on d1, 8, and bevacizumab
10 mg/kg d1 docetaxel 30mg/m2, cisplatin 25mg/m2 and irinotecan
50mg/m2 on d1, 8, and bevacizumab 10 mg/kg d1. Cycles were 3 weeks.
Response assessment - q6wks (RECIST 1.1). Primary endpoint was PFS.
Results: 85 patients: median age�61 (40-85); male/female� 70/15;
ECOG: 0/1/2�(34/49/2); gastric/GE junction/esophageal�27/21/37; measurable/evaluable:
78/7; sites of metastatic disease (# of pts): lymph nodes
(34), liver (31), lung (11), bone (5), abdomen (4), peritoneum (4), other
(11). There were two treatment-related deaths: esophageal hemorrhage,
sudden death (both TPCA). Conclusions: Both regimens were efficacious
and reasonably well tolerated. The addition of docetaxel to the attenuated
PCA combination did not significantly improve efficacy.
PCA (N�44) TPCA (N�41) P value
Major response 56.8% (41.0, 71.7) 48.8% (32.9, 64.9) 0.518
PFS median (N�85) 7.7mos (5.8, 10.1) 8.4mos (6.8, 9.8) 0.861
OS 1-year (N�85) 52.6% (36.0, 66.8) 59.1% (42.2, 72.7) 0.866
OS median (N�85)
Grade III-IV toxicity %
12.5mos (9.6, 15.5) 13.3mos (11.5, 15.4) 0.866
Neutropenia 25.0 31.7 0.492
Thrombocytopenia 4.5 4.9 1.000
Diarrhea 22.7 31.7 0.465
Fatigue 15.9 19.5 0.778
Vomiting 9.1 12.2 0.733
Infection 11.4 7.3 0.714
Anorexia 2.3 9.8 0.192
Thromboembolic 4.5 9.8 0.423
HTN 4.5 4.9 1.000
4029 Poster Discussion Session (Board #21), Mon, 1:15 PM-5:15 PM and
4:45 PM-5:45 PM
The pattern and timing of disease recurrence in squamous cancer of the
anus: Mature results from the NCRI ACT II trial. Presenting Author: David
Sebag-Montefiore, St James Institute of Oncology, Leeds, United Kingdom
Background: Concurrent chemoradiation (CRT) is standard treatment for
patients with squamous cell carcinoma of the anus. Although the majority
of patients achieve long term disease control, locoregional failure is either
detected early (failure to enter complete remission) or at a later date as
locoregional recurrence. We explore the pattern and timing of disease
recurrence within a phase III trial (ACT II), which mandated standardised
radiation fields and doses (50.4Gy in 28 daily fractions). Methods: The UK
ACT II trial recruited a total of 940 patients (2000 -2008) and compared
cisplatin with mitomycin when combined with 5flurouracil CRT and two
cycles of maintenance chemotherapy versus no maintenance using a
factorial 2x2 design. Patient characterstics: T1/2 52%, T3/4 46%; N�
32% N0 62%. The loco-regional response to treatment was assessed by
clinical examination at 11, 18 and 26 weeks after CRT. Clinical examination
was performed every two months for year 1; 3-monthly for year 2; then
6-monthly for years 3-5. CT scans of chest/abdomen/pelvis were performed
at 6,12 24 months. Sites of failure were recorded on a case record form
(primary site [PS], inguinal [ING], pelvic nodes [PEL], metastatic [METS].
Results: After a median follow up of 5 years, the crude pelvic failure (PF)
rate is 18% (163/924). Of the 163 PF, 133 pts (82%) were pelvic only and
30 (18%) had PF � metastasis. 93% of all pelvic recurrences were
detected during the first three years (54% yr 1, 26% yr 2 and 13% yr 3).
The pattern was similar for PF only and PF � mets (data not shown). Only
46 (4%) of patients had [METS] as the first disease related event. 117/133
(88%) patients with PF only are evaluable for analysis of the pattern of
failure., 53% occurred at the primary site (PS) only, 23% were PS � nodal
(5% [ING] 13% [PEL] and 5% [ING�PEL], and 25% nodal only (6%
[ING],14% [PEL] and 5% [ING�PEL]). Conclusions: The ACT II trial results
with mature follow-up demonstrate a low rate of pelvic failure. Intensive
follow up to detect potentially salvageable pelvic failure should be
restricted to a maximum of three years in future trials as only 7% of
relapses occur beyond this time point.
Gastrointestinal (Noncolorectal) Cancer
245s
4028 Poster Discussion Session (Board #20), Mon, 1:15 PM-5:15 PM and
4:45 PM-5:45 PM
A randomized phase II study of continuous versus intermittent S-1 plus
oxaliplatin in first-line treatment of patients with metastatic gastric
carcinoma. Presenting Author: Sook Ryun Park, Center for Gastric Cancer,
National Cancer Center, Goyang, Gyeonggi, South Korea
Background: We conducted a randomized phase II study to compare
continuous vs. intermittent S-1 � oxaliplatin (SOX) after induction of 6
cycles of SOX in patients (pts) with metastatic gastric cancer (MGC).
Methods: Pts �18 yrs with chemo-naive MGC, normal organ function,
ECOG PS 0-2, and measurable or evaluable lesion(s) were initially given an
induction treatment of 6 cycles of SOX (S-1 40 mg/m2 bid on D1-14 �
oxaliplatin 130 mg/m2 on D1 q 3 wks). Pts with CR/PR or SD were
randomized to continue SOX (arm A) until progression/intolerable toxicity
or discontinue until progression when SOX was re-administered (arm B).
The primary endpoint was overall survival (OS), and secondary endpoints
included progression-free survival (PFS), response rate, safety, quality of
life, and biomarker correlative studies. Results: From July 2007 to Dec
2010, a total of 250 pts entered into the study. Median age was 53 yrs
(range, 24-69); PS 0/1/2�13/219/18; M/F�162/88. Three pts did not
receive treatment and 126 (50.4%) discontinued treatment before or at
the completion of 6 cycles of SOX due to progression (45.6%), pt refusal
(2.8%), or adverse events (2.0%). A total of 121 pts were randomized: 59
(48.8%) to arm A and 62 (51.2%) to arm B. Clinical characteristics were
well balanced between arms. SOX continuation resulted in a significant
reduction in the risk of progression (median PFS, 10.5 months for arm A vs.
7.2 months for arm B; HR�0.57, 95% CI 0.39-0.84, p�0.005). With a
median follow-up of 34.0 months (range, 10.5-53.3 months), there was no
significant difference in OS (median OS, 22.6 months for arm A vs. 22.7
months for arm B; HR, 0.79, 95% CI 0.51-1.25, p�0.31). Arm A had
higher rates of grade 3/4 fatigue (28.8% vs. 8.1%, p�0.004) and
neuropathy (25.4% vs. 8.1%, p�0.014) but other grade 3/4 hematologic
(neutropenia, 35.6% vs. 32.3%; thrombocytopenia, 23.7% vs. 21.0%;
anemia, 15.3% vs. 6.5%) or non-hematologic toxicity rates were not
significantly different. Conclusions: Continuous chemotherapy with SOX
after induction therapy improved PFS but not OS. Supported by NCC Grant
1010180 (S-1 and oxaliplatin was provided by JEIL Pharm. Co., Ltd. and
sanofi-aventis Korea Co., Ltd., respectively).
4030 Poster Discussion Session (Board #22), Mon, 1:15 PM-5:15 PM and
4:45 PM-5:45 PM
Phase II trials of cetuximab (CX) plus cisplatin (CDDP), 5-fluorouracil
(5-FU) and radiation (RT) in immunocompetent (ECOG 3205) and HIVpositive
(AMC045) patients with squamous cell carcinoma of the anal
canal (SCAC): Safety and preliminary efficacy results. Presenting Author:
Madhur Garg, Albert Einstein College of Medicine/Montefiore Medical
Center, Bronx, NY
Background: Epidermal growth factor receptor (EGFR) expression and HPV
infection are common in SCAC. We therefore initiated 2 phase II studies to
evaluate the safety and efficacy of the EGFR inhibitor CX given concurrently
with CDDP/5-FU/RT in HIV-positive (AMC045) and immunocompetent
(E3205) patients with SCAC. Methods: All patients received CX (400
mg/m2 loading, then 250 mg/m2/wk IV x 6-8 wks) plus CDDP (75 mg/m2
IV q28 days x 2) and 5-FU (1000 mg/m2/day IV infusion days 1-4 q 28
days x 2) concurrently with RT (45-54 Gy) beginning with CX dose 2.
Patients in E3205 also received 2 cycles of CDDP/5-FU alone prior to
CX/CDDP/5-FU/RT; this was discontinued on recommendation of the NCI
Anorectal Task Force after 28 patients. Both trials were powered to detect a
reduction in 3-year local-regional failure (LRF) rate from 35% to 17.5%
(alpha�0.10, beta�0.10), the primary end point. Other endpoints included
progression free survival (PFS) and overall survival (OS). The results
below include complete toxicity and preliminary efficacy data (including
only the first 28 patients from E3205). Results: Expedited reporting was
required for type I (any grade 5, grade 4 cardiac) or II (grade 4 RT skin,
diarrhea) adverse events, with prespecified rates of �5% or �20%,
respectively defined as unacceptable. Early stopping rules were not invoked
for either trial. LRF rates data will be presented after more detailed case
review is completed. Conclusions: CX plus CDDP/5-FU/RT is feasible in
patients with SCAC, including patients with HIV infection. Preliminary
safety and efficacy data appear encouraging, but accrual without neoadjuvant
CDDP/5-FU continues in E3205, and additional followup of both
study cohorts is required in order to determine whether pre-specified
efficacy endpoints were met.
AMC045 E3205
No. 45 28
Stage I/II/III 24%/42%/34% 11%/50%/39%
Completed protocol therapy 37 (82%) 22 (79%)
Type I/II adverse events 2 (4%)/0 1 (4%)/1 (4%)
Colostomy rate 7% (1-18%) 14% (4-33%)
2 year PFS rate (95% CI) 80% (61-90%) 92% (81-100%)
2 year OS rate (95% CI) 89% (73-96%) 93% (83-100%)
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