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

256s Gastrointestinal (Noncolorectal) Cancer
4071 General Poster Session (Board #44F), Mon, 8:00 AM-12:00 PM
Efficacy and safety of bevacizumab combined with capecitabine in progressive,
metastatic well-differentiated digestive endocrine tumors (BETTER
study). Presenting Author: Emmanuel Mitry, Institut Curie, St. Cloud,
France
Background: Neuroendocrine digestive tumors are highly vascularized
neoplasms known to express the vascular endothelial growth factor (VEGF).
We assessed the activity of bevacizumab (Bv), a monoclonal antibody
directed against VEGF combined with capecitabine (CAP). Methods: In this
multicenter, open-label, non-randomized, two-group phase II trial, one
group assessed Bv (7.5 mg/m² on d1/3 weeks) combined with CAP (1,000
mg/m2 twice daily, orally d1-14, resumed on day 22). Eligible patients (pts)
had progressive, metastatic well-differentiateddigestive tract endocrine
tumors (WHO 2000 classification), ECOG-PS �2, Ki 67 index � 15%, no
prior systemic chemotherapy and acceptable organ functions. The primary
endpoint was progression-free survival (PFS). Secondary endpoints were
overall survival, response rate, safety and quality of life. Pts were treated for
a minimum of 6 months and study duration was 24 months. Results: From
Jun 2007 to Oct 2009, 49 pts were enrolled, 26 (53.1%) were men;
median age 60.3 years (41.2-82.3); ECOG-PS was 0/1 in 46 (93.9%) pts.
Primary tumor site was: small intestine 40 (81.6%) pts, caecum 3 (6.1%),
rectum 4 (8.2%) and stomach 2 (4.1%). Ki-67 proliferative index was
0-2% in 17 (35.4%) pts, 3-4% in 14 (29.2%), 5-9% in 13 (27.1%),
10-14% in 4 (8.3%) Metastatic sites were liver: 46 (93.9%) pts, lymph
nodes: 24 (49.0%), peritoneum 23 (46.9%). Median treatment duration
was 13.8 months; median number of cycles was 19. At 24 months, median
PFS was 23.4 months [95%CI: 13.2; not reached] based on 26 events.
PFS rate at 18 months was 55%. Tumor control rate was 87.8% (n�43)
including partial response in 9 (18.4%) pts and stable disease in 34
(69.4%) pts. Survival rate at 24 months was 85%, median overall survival
was not reached, 8 patients died. CTC grade 3/4 Adverse Events (AEs)
occurred in 41 (83.7%) pts, mainly digestive 14 (28.6%) pts. Main G3/4
Bv targeted AE was hypertension in 15 (30.6%) pts. Conclusions: In this
chemotherapy resistant tumor, the combination of capecitabine and
bevacizumab, assessed in a phase II study, shows such encouraging results
that this combination may become a reference in the medical treatment of
ileal NET.
4073 General Poster Session (Board #44H), Mon, 8:00 AM-12:00 PM
Cetuximab, paclitaxel, cisplatin and concurrent radiation in Chinese
patients with locally advanced esophageal squamous cell carcinoma: An
open-label, multicenter, phase II study. Presenting Author: Jinming Yu,
Department of Radiation Oncology, Shandong Cancer Hospital and Institute,
Jinan, China
Background: In China more than 90% of esophageal malignancies are of
squamous cell carcinoma (SCC). We conducted this Chinese multicenter
trial to determine the efficacy and safety of the addition of cetuximab with
paclitaxel, cisplatin, and concurrent radiation for patients with esophageal
SCC and to determine whether KRAS status predicts response. Methods:
Patients with unresectable locally advanced cervical, upper or midesophageal
SCC without distant metastasis were eligible for this open-label
phase II trial. All patients received cetuximab (400 mg/m2 day 1 before
chemoradiotherapy and 250 mg/m2 q1w � 7 weeks), paclitaxel (45 mg/m2 q1w � 7 weeks) and cisplatin (20 mg/m2 q1w � 7 weeks) with 59.4 Gy of
radiation. The primary end point was response rate. Second end points
included toxicity, overall survival (OS), progression-free survival (PFS), and
KRAS mutation status. Results: Fifty-five patients were enrolled and
evaluable to safety. Non-hematological adverse events were generally grade
1 or 2, and were most often rash (94.5%), mucositis (58.2%), fatigue
(45.5%), nausea (41.8%) and hepatic dyfunction (40%). Hematologic
adverse events included grade 3 neutropenia (32.7%) and grade 3 anemia
(1.82%). Ten patients did not complete the protocol therapy (6 for
chemotherapy dose delays, 1 for paciltaxel hypersensitivity, 1 by the
treating physicians for unstated reasons, 1 for concurrent unrelated
infection, and 1 for tracheo-esophageal fistula). The response rate was
97.7%. The 1-year OS and median OS was 87.3% and 16.8 months, the
1-year PFS and median PFS was 30.4% and 13.9 months, respectively. No
mutations were detected at KRAS codons 12 or 13 in the 52 available
specimens. Conclusions: Cetuximab can be safely administered with
chemoradiation for Chinese patients with esophageal cancer and may
improve the clinical response rate. KRAS mutations were too rare to be
analyzed as a predictor of response.
4072 General Poster Session (Board #44G), Mon, 8:00 AM-12:00 PM
NeoFLOT: Multicenter phase II study of perioperative chemotherapy in
resectable adenocarcinoma of the gastroesophageal junction or gastric
adenocarcinoma. Presenting Author: Christoph Schulz, Department of
Hematology and Oncology, Klinikum Grosshadern and Comprehensive
Cancer Center, LMU Munich, Munich, Germany
Background: The rationale of the NeoFLOT-trial was the intensification of
neoadjuvant chemotherapy (NACT) by prolongation of preoperative treatment.
This strategy is based on the notion that while perioperative
treatment is notably beneficial in locally advanced gastroesophageal cancer
(GEC), postoperative chemotherapy can only be applied in a fraction of
patients (pts). Methods: Pts with T3, T4 and/or N� adenocarcinoma (GEC)
were eligible for this multicenter phase II trial. NACT consisted of 6 cycles
of oxaliplatin 85 mg/m2 , leucovorin 200 mg/m2 , fluorouracil 2600 mg/m2 and docetaxel 50 mg/m2 (FLOT) applied q 2 wks. Staging was performed
after 3 cycles to select pts with progressive disease (PD) for immediate
surgery. Primary endpoint was the R0-resection rate. Secondary endpoints
included the pathological complete response rate (pCR), histologic tumor
regression grade (Becker 2003), safety, and progression-free survival
(PFS). Results: From 10/2009 to 06/2011, 59 pts were enrolled of whom
58 pts were assessable for safety. Median age was 61 years (range: 32-79),
58.6% (34/58) had tumors of the gastroesophageal junction. 50 pts
underwent surgery and were assessable for the primary endpoint. R0resection
rate was 86.0% (43/50). pCR was achieved in 20.0% (10/50) of
pts. During NACT, 6.9% (4/58) of pts developed progressive disease. Dose
reduction was performed in 43.1% (25/58) of pts resulting in a median
dose intensity of 89.2%. Grade 3/4 neutropenia was observed in 29.3%
(17/58) of pts, febrile neutropenia grade 3/4 in 1.7% (1/58). Common
grade 3/4 non-hematologic adverse events were diarrhea (13.8% (8/58))
and mucositis (6.9% (4/58)). Treatment related mortality was 3.4% (2/58)
with 2 cases of sepsis. After a median follow-up of 9.1 months, median PFS
and OS have not been reached. Conclusions: These data indicate that NACT
with 6 cycles FLOT is well-tolerated and highly effective in resectable GEC.
4074 General Poster Session (Board #45A), Mon, 8:00 AM-12:00 PM
Oxaliplatin, irinotecan, bevacizumab followed by docetaxel, bevacizumab
in inoperable gastric cancer: First efficacy results of a multicenter phase II
trial (AGMT Gastric-3) of the Arbeitsgemeinschaft Medikamentöse Tumortherapie.
Presenting Author: Ewald Woell, St. Vinzenz Krankenhaus Betriebs
GmbH, Zams, Austria
Background: In our previous phase II trials (AGMT-Gastric-1 and AGMT
Gastric-2) efficacy of oxaliplatin and irinotecan as well as oxaliplatin,
irinotecan and cetuximab was shown. Time to progression however was
short suggesting acquired chemotherapy resistance. Therefore sequential
chemotherapy combined with bevacizumab is investigated in the presented
trial. Methods: Oxaliplatin 85 mg/m2 biweekly (q2w) and irinotecan 125
mg/m2 q2w are administered for the first three months followed by
docetaxel 50mg/m2 q2w for three months. Chemotherapy for 6 months is
combined with bevacizumab 5 mg/kg q2w which is administered until
progression. For this abstract 36 patients (pt.) with histologically proven
unresectable and/or metastatic gastric adenocarcinoma have been evaluated
in a first line setting. Median age: 62.5 years (range 26-80 years), PS
0: 25 patients, PS 1: 10 patients, missing: 1 patient, single metastatic
site: 24 patients, multiple metastases: 10 patients, missing: 2. Results:
Frequently reported adverse events (more than 20% of pt.) were predominantly
grade 1 or 2 and included diarrhea (25/36, 69%), polyneuropathy
(17/36, 47%), nausea (17/36, 47%), fatigue (15/36, 42%), neutropenia
(13/36, 36%), abdominal pain (11/36, 31%), hypokalemia (9/36, 25%).
Grade 3 and 4 toxicities included neutropenia (6/36, 17%), diarrhea
(3/36, 8%), hypokalemia (3/36, 8%), anemia in (2/36, 6%), leucopenia
(2/36, 6%), thrombocytopenia (1/36, 3%), nausea in (1/36, 3%). Objective
response rate after 3 cycles was available in 25 patients: CR 1/25
(4%), PR 14/25 (56%), SD 8/25 (32%), PD 2/25 (8%). After 6 cycles
there were 12 evaluable patients with CR 2/12 (16.7%), PR 5/12 (41.7%),
SD 4/12 (33.3%) and PD 1/12 (8.3%). Conclusions: The combination of
oxaliplatin and irinotecan with bevacizumab followed by docetaxel with
bevacizumab is feasible and very active in advanced gastric cancer.
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