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

478s Lung Cancer—Non-small Cell Local-Regional/Small Cell/Other Thoracic Cancers
7108 General Poster Session (Board #43C), Sat, 1:15 PM-5:15 PM
Factors influencing outcome in thymic epithelial tumors (TET). Presenting
Author: Ryan Frederick Porter, Indiana University School of Medicine,
Indianapolis, IN
Background: TET represent a heterogeneous collection of rare tumors,
thymoma and thymic carcinoma (TC). Prognosis is often based on WHO
histology and Masaoka Stage (MS) with small series often lacking long-term
follow-up or advance stage disease. We examined predictors of relapse,
disease-free survival (DFS) and overall survival (OS) based on WHO
classification and MS. Methods: A retrospective analysis was performed on
patients(pts) with TET seen at IUSCC from 1976 to 2011 with available
tissue blocks. MS, WHO histology, demographics, autoimmune coexistence
and non-TET neoplasms were correlated with DFS and OS (via
Kaplan-Meier analysis). Results: Of 251 pts identified, MS at diagnosis was
I(n�74), II(n�43), III(n�71), IVa(n�38), IVb(n�12) and indeterminate
(n�13). The histology were thymoma (n�195) and TC (n�56). Median age
was 51(10-88) and (M:F �121:130). Autoimmune disease was present
(n�82) (myasthenia gravis n�52) and non-TET neoplasms (n�36).
Therapy after diagnosis included surgery alone (n�115), radiation (n�29),
chemo (n�71), chemo-radiotherapy (n�29), indeterminate(n�7). Median
follow up was 69 months (1 to 399.5). DFS for stages I,II,III at 5 years was
83%, 71% and 39%; DFS was associated with MS (p�.001) and WHO
classification (p�.028). The 5yr and 10yr OS for stages I, II, III, IVa, IVb
were 90%, 94%, 80%, 55%, 14% and 65%, 52%, 53%, 28%, 0%. The
5yr OS for WHO classification were: A/AB-89%, B1/B2/B3-98% and
C-30% and 10yr survivals were 89%, 62%, 0%. OS was associated with
MS (p�.01) , WHO classification (p�.001) and autoimmune disease
(p�.03). Late relapses (�5yr) occurred in 13 (23%) pts, including 3 with
Stage I and 2 with WHO A classification. Conclusions: MS, WHO classification
and autoimmune disorders were statistically significant with OS and
with DFS for MS and WHO. TC prognosis is significantly worse than
thymoma. The improved OS with autoimmune disease requires further
investigation but raises the possibility of benefit derived from earlier
diagnosis and/or heightened immune surveillance. These data support the
notion that all TET, regardless of histologic subtype or clinical stage, are
malignant with a capacity for metastasis. As relapses beyond 5 years are
common, lifelong follow-up for TET is recommended.
TPS7110 General Poster Session (Board #43E), Sat, 1:15 PM-5:15 PM
Vinorelbine plus cisplatin versus gefitinib in resected non-small cell lung
cancer haboring activating EGFR mutation (WJOG6410L). Presenting
Author: Hirohito Tada, Department of General Thoracic Surgery, Osaka City
General Hospital, Osaka, Japan
Background: Vinorelbine plus cisplatin after completely resected stage II-III
non-small cell lung cancer (NSCLC) is a standard therapy. Stage IV
non-small cell lung cancer (NSCLC) harboring mutations in the epidermal
growth factor receptor (EGFR) is quite sensitive to tyrosine kinase inhibitors
(TKIs). Three randomized trials demonstrated that gefitinib is superior to
platinum based chemotherapy in progression free survival. Retrospective
analysis of adjuvant TKIs therapy for patient with resected lung cancer
harboring EGFR mutation showed favorable trend toward improvement in
disease free survival (DFS) and overall survival (OS). (J Thorac Oncol.
2011;6: 569–575) BR19 comparing adjuvant gefitinib vs. placebo for
completely resected NSCLC without any selection of biomarker was closed
early and did not show any benefit of adjuvant gefitinib, even in the EGFR
mutation positive cohort. The randomized trial in adjuvant therapy with
erlotinib vs. placebo for patients with overexpression of EGFR protein has
complete enrolment already. We conduct the first randomized phase III
trial comparing adjuvant gefitinib with chemotherapy in patients with
completely resected stage II-III NSCLC harboring EGFR mutations. Methods:
Patients who have undergone complete resection and have EGFR mutation,
deletions in exon 19, or L858R point mutation at exon 21 and without
T790M mutation are randomly assigned gefitinib 250mg a day for 2 years
or vinorelbine 25mg/m2 days 1 and 8, plus cisplatin 80mg/m2 day 1, every
3 weeks for 4 courses. The primary endpoint is DFS and secondary
endpoints are OS and safety. On the basis of previous studies, we assume
the hazard ratio of DFS is 0.65. To demonstrate this improvement in DFS,
230 patients in total would be needed during 3-year accrual period. This
trial has begun from September 12 among 22 institutes in Japan. Until now
(January 31. 2012), 13 cases have been enrolled. Five cases were enrolled
in latest 1 month.
TPS7109 General Poster Session (Board #43D), Sat, 1:15 PM-5:15 PM
International tailored chemotherapy adjuvant trial: Itaca trial. Presenting
Author: Silvia Novello, University of Turin, Orbassano, Italy
Background: This is an ongoing phase III multicenter randomized trial
comparing adjuvant pharmacogenomic-driven chemotherapy, based on
thymidilate synthase (TS) and excision-repair cross-complementing -1
(ERCC1) gene expression versus standard adjuvant chemotherapy in
completely resected stage II-IIIA non-small cell lung cancer (EudraCT #:
2008-001764-36). Methods: In all registered patients, before randomization,
expression of ERCC1 and TS is assessed by qRT-PCR on paraffinembedded
tumor specimens in a central laboratory. Randomization is
stratified by stage and smoking status. Trial was emended on Feb, 2011
with the 7th staging system. Primary end point is overall survival; secondary
end points include recurrence-free survival, therapeutic compliance, toxicity
profile and comparative evaluation of ERCC1 and TS mRNA versus
protein. It is assumed that the 5-year survival in the control arm is 45% and
the hazard reduction associated to the experimental treatment is 30%.
With a power of 90% to detect the estimated effect with log-rank test, a
significant level of 5% (2 tails), 336 events have to be observed; the
expected total number of patients is 700. The final statistical analysis will
group together all control arms and all tailored chemotherapies groups.
Efficacy analysis will be done on an intent-to-treat basis. Cox proportional
hazard model will be used for estimating hazard ratios after adjusting for
relevant variables. Within 45 days post-surgery, patients in each genetic
profile are randomized to receive either a standard chemotherapy selected
by the investigator (cisplatin/vinorelbine, cisplatin/docetaxel or cisplatin/
gemcitabine) or an experimental treatment (tailored arms) selected as
follows: 1) high ERCC1 and high TS 4 cycles of single agent paclitaxel 2)
high ERCC1 and low TS 4 cycles of single agent pemetrexed 3) low ERCC1
and high TS 4 cycles of cisplatin/gemcitabine 4) low ERCC1 and low TS) 4
cycles of cisplatin/pemetrexed. All chemotherapy regimens are administered
for a total of 4 cycles on a 3-weekly basis. Currently, 312 patients
have been randomized from 26 institutions mainly located in Italy and
Germany (average enrolment: 13 patients/month).
TPS7111 General Poster Session (Board #43F), Sat, 1:15 PM-5:15 PM
Postoperative follow-up of lung cancer: Randomized trial comparing two
follow-up programs in completely resected non-small cell lung cancer
(IFCT-0302). Presenting Author: Virginie Westeel, Besançon University
Hospital, Besançon, France
Background: There are no robust data published on the follow-up after
surgery for non-small cell lung cancer (NSCLC). Current international
guidelines are informed by expert opinion. Most of them recommend
regular follow-up with clinic visit and thoracic imaging, either chest X-ray of
Chest CT-scan. The IFCT-0302 trial addresses the question whether a
surveillance program with chest CT-scan and fiberoptic bronchoscopy can
improve survival compared to a follow-up only based on physical examination
and chest x-ray. There is no such trial ongoing over the world. Methods:
The IFCT-0302 trial is a multicenter open-label controlled randomized
phase III trial. The objective of the trial is to compare two follow-up
programs after surgery for stage I-IIIa NSCLC. The primary endpoint is
overall survival. Patients are randomly assigned to arm 1, minimal
follow-up, including physical examination and chest x-ray; or arm 2, a
follow-up consisting of physical examination and chest x-ray plus chest CT
scan and fiberoptic bronchoscopy (optional for adenocarcinomas). In both
arms, follow-up procedures are performed every 6 months during the first
two postoperative years, and every year between the third and the fifth
years. The main eligibility criteria include: completely resected stage I-IIIA
(6th UICC TNM classification) or T4 (in case of nodules in the same lobe as
the tumor) N0 M0 NSCLC, surgery within the previous 8 weeks. Patients
who have received and/or who will receive pre/post-operative chemotherapy
and/or radiotherapy are eligible. Statistical considerations: 1,744 patients
is required. Accrual status: 1,568 patients from 119 French centers had
been included. The end of accrual can be expected for September 2012.
Ancillary study: Blood samples are collected in 1000 patients for genomic
high density SNP micro-array analysis. This collection will contribute to the
French genome wide association study (gwas) of lung cancer gene susceptibility,
and the genetic factors predictive of survival and lung cancer
recurrence will be analyzed.
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