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

460s Lung Cancer—Non-small Cell Local-Regional/Small Cell/Other Thoracic Cancers
7034 General Poster Session (Board #34A), Sat, 1:15 PM-5:15 PM
Epidermal growth factor receptor mutation status and adjuvant chemotherapy
in resected advanced non-small cell lung cancer. Presenting
Author: Si-Yu Wang, Cancer Center, Sun Yat-sen University, Guangzhou,
China
Background: Mutations in the epidermal growth factor receptor (EGFR) are
associated with response to chemotherapy in patients with advance
NSCLC. The purpose of this study was to assess the association of
mutations in the EGFR tyrosine kinase domain and the efficacy of adjuvant
chemotherapy in patients with fully resected IIIA-N2 NSCLC tumors.
Methods: Tumor samples (n �150) from patients in our prior trial with
IIIA-N2 NSCLC who either had or had not received paclitaxel/vinorelbine
plus carboplatin chemotherapy following removal of the tumor were
analyzed for EGFR mutations in exons 19 and 21. The association of the
presence of EGFR mutations and survival following treatment was assessed.
Results: Mutations were identified in 33 (22%) patients (n�13 in
the no chemotherapy [observation] arm and n�20 in the chemotherapy
arm). Fourteen patients (9.3%) had deletion mutations in exon 19, and 19
patients (12.7%) had a substitution mutation in exon 21. Compared with
patients wild-type for EGFR, patients with EGFR mutations had numerical
but not statistically significant improved disease-free survival (35 months
[95% CI, 14.6-55.4] versus 23 months [95% CI, 17.3-28.7], respectively,
P�0.339) and overall survival (36 months [95% CI, 27.9 to 44.1] versus
26 months [95% CI, 20.1 to 31.9], respectively p�0.271) regardless of
treatment. Patients with wild-type EGFR had greater overall survival with
chemotherapy compared to no adjuvant therapy (HR�1.920; 95%CI,
1.245-2.963; p�0.003). In contrast, EGFR mutant patients in the
observation group compared to the chemotherapy group had longer median
disease-free survival (35 months [95% CI, 20.9 to 49.1] versus 27 months
[95% CI, 5.3 to 48.7], respectively, p�0.671) and overall survival (33
months [95% CI, 24.2 to 41.8] versus 40 months [95% CI, 31.8 to 48.2]
respectively, p �0.360). Conclusions: In this study, the status of mutations
in exons 19 and 21 of EGFR was associated with different clinical
outcomes in patients with resected IIIA-N2 NSCLC tumors either treated
with or without adjuvant chemotherapy. These findings suggest that a
patient’s treatment should be customized to their EGFR mutational status.
7036 General Poster Session (Board #34C), Sat, 1:15 PM-5:15 PM
Intrapleural combination bevacizumab with cisplatin therapy for non-small
cell lung cancer caused by non-small cell lung cancer. Presenting Author:
Nan Du, Department of Oncology, First Affiliated Hospital, Chinese PLA
General Hospital, Beijing, China
Background: Malignant pleural effusion (MPE) is a common complicate of
advanced non-small cell lung cancer (NSCLC). Bevacizumab, a humanized
monoclonal antibody to VEGF, has been shown to be efficient in suppressing
the pleural fluid accumulation; however, it has not been reported that
whether bevacizumab can be used intrapleurally for the treatment of MPE.
The present study is to evaluate the efficacy and safety of combined
intrapleural therapy with bevacizumab and cisplatin, an antineoplastic
agent, in controlling MPE. Methods: A total of 65 NSCLC patients with MPE
were randomly assigned to one of two groups: intrapleural bevacizumab
(300mg) with cisplatin (60mg) therapy (n�35) and intrapleural cisplatin
(60mg) therapy (n�30). Results: The curative efficacy following combination
or cisplatin mono therapy were 85.71% and 56.67%, respectively,
being combination therapy group (p�0.05) is significantly higher. In
addition, the combination therapy showed a higher efficacy in the patients
with VEGF positive (p�0.01). Among the 25 cases that showed initial
resistance to chemotherapy, 22 responded well to the combination
therapy. Furthermore, combined bevacizumab with cisplatin therapy significantly
reduced the VEGF expression, as shown by quantitative RT-PCR. All
procedures were well tolerated by the patients, with wwwno severe side
effect detected. Conclusions: Intrapleural combined bevacizumab with
cisplatin therapy was effective and safe in managing MPE caused by
NSCLC; the expression level of VEGF in MPE can be a prognostic marker for
bevacizumab therapy.
7035 General Poster Session (Board #34B), Sat, 1:15 PM-5:15 PM
Adjuvant carboplatin, docetaxel, bevacizumab, and erlotinib versus chemotherapy
alone in patients with resected non-small cell lung cancer: A
randomized phase II study of the Sarah Cannon Research Institute (SCRI).
Presenting Author: David Michael Waterhouse, Oncology Hematology
Care/SCRI, Cincinnati, OH
Background: Adjuvant chemotherapy improves overall survival (OS) in
patients (pts) with resected non small cell lung cancer (NSCLC). Bevacizumab
and erlotinib improve survival in pts with advanced unresectable
NSCLC. This randomized phase II multicenter pilot study examined the
safety and efficacy of chemotherapy and bevacizumab followed by bevacizumab
and erlotinib vs. chemotherapy alone in pts with resected NSCLC.
Methods: Eligible pts had completely resected (R0) stage IB, II, or IIIA
NSCLC (TNM 6th Ed.), any NSCLC histology, and an ECOG PS 0-1. Pts were
excluded for preoperatively confirmed N2 disease; N2 disease found at
surgery was allowed. Pts were randomized 1:1 to carboplatin AUC�5,
docetaxel 60 mg/m2 , and bevacizumab 15 mg/kg IV d1 q 21 days x 4,
followed by maintenance bevacizumab 15 mg/kg d1 and erlotinib 150 mg
PO daily x 8 cycles (Arm A) or carboplatin AUC�6 and docetaxel 75 mg/m2 IV d1 q 21 days x 4 (Arm B). The primary endpoint was 1-year disease-free
survival (DFS); safety, 2-year DFS, and OS were secondary endpoints.
Results: 106 pts were enrolled from 2/2008 to trial closure 1/2012 (A�54;
B�52). Baseline features were balanced: age 63 yrs (42–87); 54% male;
IB (46%), IIA (8%), IIB (27%), IIIA (18%); adenocarcinoma (61%),
squamous (31%). Arm A received a median of 7 cycles (1-12); Arm B 4
cycles (1-4). 1- and 2-year DFS by stage are shown in the table. The 1-year
DFS for all stages were 78% (A) and 88% (B) (p�.66). The 3-year OS for all
stages were 81% (A) and 63% (B). Neutropenia was the most common
grade 3/4 hematologic toxicity (A 18%; B 29%). Severe non-hematologic
toxicity was rare: fatigue (A 6%), diarrhea (B 6%). Bronchopleural fistulae
occurred in 2 pts (1 per arm), and grade 3 gastrointestinal hemorrhage was
seen in 1 pt (A). Conclusions: This pilot study demonstrated that bevacizumab
and erlotinib could be safely added to platinum-doublet chemotherapy
in the adjuvant setting in all histologies. Larger randomized studies
will best define the roles of these agents in pts with resectable NSCLC.
IB II IIIA
A B A B A B
N�24 N�25 N�19 N�19 N�11 N�8
1-year DFS 93% 91% 83% 100% 100% 83%
2-year DFS 84% 91% 71% 83% 75% 83%
7039 General Poster Session (Board #34F), Sat, 1:15 PM-5:15 PM
A prospective phase II study of induction erlotinib therapy in stage IIIA-N2
non-small cell lung cancer. Presenting Author: Wenzhao Zhong, Guangdong
Lung Cancer Institute, Guangdong General Hospital and Guangdong
Academy of Medical Sciences, Guangzhou, China
Background: Stage IIIA NSCLC represents a heterogeneous group of
patients with ipsilateral mediastinal (N2) lymph nodes involvement. The
epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs)
provide dramatic responses in patients with non-small cell lung cancer
(NSCLC) carrying EGFR mutations. The purpose of this study is to evaluate
the role of induction EGFR-TKI therapy in IIIA-N2 NSCLC. Methods:
Patients with resectable NSCLC of stage IIIA-N2 were assigned to either
induction erlotinib arm or induction gemcitabine/carboplatin(GC) arm
based on the EGFR mutations analysis (NCT00600587) . Study Design:
Phase II, factorial Assignment, Safety/Efficacy; Primary outcome measures:
Response to Induction Therapy; Estimated enrollment: 5 cases with
partial response in the erlotinib arm. Results: From January 2008 till June
2011, 24 patients with IIIA-N2 NSCLC diagnosed by mediastinoscopy or
PET/CT have been enrolled. Twelve cases with EGFR mutation were
assigned to the erlotinib arm (30-42 days), while 12 cases harboring
wild-type EGFR received the GC regimen (3 cycles). The primary end point
of the response rates were 58% (7/12) for the erlotinib arm and 33% (4/12)
for the GC arm (P�0.49). The pathological N2 complete response rates
were 17% for the erlotinib arm and 25% for the GC arm (P�0.64). In the
erlotinib arm, the most common failure model after initial therapy was
distant metastases (9/10), especially brain metastases (3/9). The median
progression free survival time was 7 months for the erlotinib arm and 9
months for the GC arm (P�0.27). The median overall survival was 27
months for the erlotinib arm and 23 months for the GC arm (P�0.52). In
addition, four cases in the erlotinib arm got partial response to the 2nd
EGFR-TKI therapy after progression to erlotinib induction therapy and the
following thoracotomy. Conclusions: Induction erlotinib therapy in IIIA-N2
NSCLC with EGFR activating mutation is a promising strategy. Distance
metastases were major failure model. A multicenter, randomized, phase II
study evaluating efficacy and safety of erlotinib vs GC as neoadjuvant
therapy for stage IIIA-N2 NSCLC patients with EGFR mutations
(NCT01407822) is currently recruiting participants.
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