A 15-gene expression signature prognostic for survival and predictive for adjuvant chemotherapy benefit in JBR.10 patients.

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Abstracts

2008 ASCO Annual Meeting

A 15-gene expression signature prognostic for survival and predictive for adjuvant chemotherapy benefit in JBR.10 patients.

Sub-category:

Adjuvant Therapy

Category:

Lung Cancer--Local-Regional and Adjuvant Therapy

Meeting:

2008 ASCO Annual Meeting

Abstract No:

7510

Citation:

J Clin Oncol 26: 2008 (May 20 suppl; abstr 7510)

Author(s):

M. S. Tsao, C. Zhu, K. Ding, D. Strumpf, M. Pintilie, M. Meyerson, L. Seymour, I. Jurisica, F. A. Shepherd

Abstract:

Background: The JBR.10 trial demonstrated a significant survival benefit from adjuvant chemotherapy in stage IB-II NSCLC patients (HR 0.69, p=0.04). However, a significant interaction with stage was seen, with benefit limited to stage II patients. Gene expression profiling may identify patient groups with significantly different prognosis, with potential for improved selection of patients to receive adjuvant chemotherapy. Methods: Gene expression profiling by Affymetrix U133A was performed on RNA isolated from snap-frozen banked tumor tissues of 133 (62 on observation and 71 on chemotherapy) JBR.10 patients. A minimal prognostic gene set was identified based on goodness-of-fit (R square) of the Cox proportional hazard model and leave one out cross-validation in the observation patients. Results: A 15-gene expression signature was identified that separated the 62 observation patients into groups with high (n=33) and low risk (n=29) for death (HR 60.1, p< 0.0001). This prognostic signature was validated in five independent public gene expression datasets (stage I-II patients, total n=372). Chemotherapy significantly reduced the risk of death in high-risk patients (HR 0.27, C.I. 0.14-0.51, p<0.0001). The benefit of chemotherapy was seen both in high-risk stage IB (HR 0.28, p=0.007) and stage II (HR 0.26, p=0.0059) patients, but not in low-risk patients (HR 15.49, p=0.008). Interaction of chemotherapy and expression signature was highly significant (p=0.0001). Conclusions: We have identified a 15-gene signature that is an independent prognostic marker in early stage NSCLC for identifying more selectively than stage, patients who may benefit from adjuvant chemotherapy.

Abstract Disclosures

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy and are designated with a caret symbol (^) here and in the print version.

Associated Presentation(s):

1. A 15-gene expression signature prognostic for survival and predictive for adjuvant chemotherapy benefit in JBR.10 patients

Meeting: 2008 Best of ASCO Boston
Speaker: M. Tsao
Session: General Session XIII: Lung Cancer - Non-Small Cell Carcinoma

2. A 15-gene expression signature prognostic for survival and predictive for adjuvant chemotherapy benefit in JBR.10 patients.

Meeting: 2008 ASCO Annual Meeting
Presenter: Ming S Tsao, MD, FRCPC
Session: Lung Cancer — Local-Regional and Adjuvant Therapy (Oral Presentation)

Other Abstracts in this Sub-Category:

		1. Phase III study of pemetrexed plus carboplatin (PC) versus etoposide plus carboplatin (EC) in chemonaive patients (pts) with extensive-stage disease small cell lung cancer (ED-SCLC): Interim results Meeting: 2008 ASCO Annual Meeting Abstract No: NSA First Author: M.A. Socinski Category: Lung Cancer--Local-Regional and Adjuvant Therapy - Adjuvant Therapy
		2. Use of Ras effector RASSF1A promoter gene methylation and chromosome 9p loss of heterozygosity (LOH) to predict progression-free survival (PFS) in perioperative chemotherapy (CT) phase III trial IFCT-0002 in resectable non-small cell lung cancer. Meeting: 2008 ASCO Annual Meeting Abstract No: 7500 First Author: G. Zalcman Category: Lung Cancer--Local-Regional and Adjuvant Therapy - Adjuvant Therapy
		3. Association of gene expression signature and clinical efficacy of MAGE-A3 antigen-specific cancer immunotherapeutic (ASCI) as adjuvant therapy in resected stage IB/II non-small cell lung cancer (NSCLC). Meeting: 2008 ASCO Annual Meeting Abstract No: 7501 First Author: J. F. Vansteenkiste Category: Lung Cancer--Local-Regional and Adjuvant Therapy - Adjuvant Therapy
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Abstracts by M. S. Tsao :

		1. A 15-gene expression signature prognostic for survival and predictive for adjuvant chemotherapy benefit in JBR.10 patients. Meeting: 2008 ASCO Annual Meeting Abstract No: 7510 First Author: M. S. Tsao Category: Lung Cancer--Local-Regional and Adjuvant Therapy - Adjuvant Therapy
		2. A phase II study of temsirolimus (CCI-779) in patients with metastatic and/or locally advanced recurrent endometrial cancer previously treated with chemotherapy: NCIC CTG IND 160b. Meeting: 2008 ASCO Annual Meeting Abstract No: 5516 First Author: A. M. Oza Category: Gynecologic Cancer - Uterine Cancer
		3. A phase II trial of the histone deacetylase inhibitor belinostat (PXD101) in patients with platinum resistant epithelial ovarian tumors and micropapillary/borderline (LMP) ovarian tumors. A PMH phase II consortium trial. Meeting: 2008 ASCO Annual Meeting Abstract No: 5518 First Author: H. Mackay Category: Gynecologic Cancer - Ovarian Cancer
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Presentations by M. S. Tsao :

		1. A 15-gene expression signature prognostic for survival and predictive for adjuvant chemotherapy benefit in JBR.10 patients. Meeting: 2008 ASCO Annual Meeting Presenter: Ming S Tsao, MD, FRCPC Session: Lung Cancer — Local-Regional and Adjuvant Therapy (Oral Presentation)
		2. Proceedings I Press Briefing Meeting: 2008 ASCO Annual Meeting Participant: Ming S Tsao, MD, FRCPC Session: Proceedings I Press Briefing (Press Program)
		3. Molecular Prognostic Profiles in Resected Non-Small Cell Lung Cancer: Are We Ready for Prime Time? Meeting: 2007 ASCO Annual Meeting Speaker: Ming S Tsao, MD Session: Molecular Prognostic Profiles in Resected Non-Small Cell Lung Cancer: Are We Ready for Prime Time? (Education Session)
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Educational Book Manuscripts by M. S. Tsao :

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