Pilot SCAT trial: Spanish customized adjuvant chemotherapy (CT) based on BRCA1 mRNA expression levels (l) in resected stage II-IIIA non-small cell lung cancer (NSCLC) patients (p).

Authors

null

Jose Miguel Sanchez

Hospital M. D. Anderson Internacional, Madrid, Spain

Jose Miguel Sanchez , Manuel Cobo , Rafael Arrabal , Bartomeu Massuti , Jose Manuel Rodriguez Paniagua , Teresa Moran , Julio Astudillo , Ulpiano Jimenez , Yat Wa Pun , David Aguiar Bujanda III, Jorge Freixenet , Jose-Luis Gonzalez-Larriba , Florentino Hernando-Trancho , Jose Gómez-Codina , Juan-Carlos Penalver , Natividad Martinez Banaclocha , Guillermo Lopez-Vivanco , Joaquin Pac , Miquel Taron , Rafael Rosell

Organizations

Hospital M. D. Anderson Internacional, Madrid, Spain, Hospital Regional Universitario Carlos Haya, Málaga, Spain, Thoracic Surgery Hospital Universitario Carlos Haya, Malaga, Spain, Hospital General de Alicante, Alicante, Spain, Thoracic Surgery Alicante University Hospital, Alicante, Spain, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Barcelona, Spain, Thoracic Surgery Hospital Germans Trias i Pujol Badalona, Badalona, Spain, Medical Oncology Hospital La Princesa, Madrid, Spain, Thoracic Surgery Hospital La Princesa, Madrid, Spain, Hospital Universitario Gran Canaria Dr Negrin, Las Palmas de Gran Canaria, Spain, Hospital Dr. Negrin, Las Palmas, Las Palmas de Gran Canaria, Spain, Hospital Clinico San Carlos, Madrid, Spain, Thoracic Surgery Hospital Clinico San Carlos Madrid, Madrid, Spain, Hospital La Fe, Valencia, Spain, Hospital La Fe, Valencia, Valencia, Spain, Department of Oncology, University General Hospital of Elche, Elche, Spain, Department of Medical Oncology, Hospital de Cruces, Barakaldo, Spain, Hospital de Cruces, Baracaldo, Spain

Research Funding

Other Foundation
Background: Surgical resection is the standard treatment in early stages of NSCLC. Nonetheless, long-term survival rate even after surgical resection is disappointing. Several randomized trials and meta-analyses confirmed the survival benefit of adjuvant cisplatin-based CT for stage II and IIIA. BRCA1 is a component of multiple DNA repair pathways, functions as a molecular determinant of response to cytotoxic chemotherapeutics agents, and is an independent prognostic variable in resected p. Since BRCA1 mRNA expression has been linked to differential sensitivity to cisplatin and antimicrotubule drugs, BRCA1 expression may provide additional information for customizing adjuvant CT. Methods: Completely resected p with pathological lymph node involvement (N1, N2) received 4 cycles of customized adjuvant CT according BRCA1 l. Low l: gemcitabine-cisplatin, intermediate l: docetaxel-cisplatin, high l: docetaxel. Overall survival (OS) was the primary endpoint. Multivariate analysis for time to relapse (TTR) and survival was performed. Results: Eighty-three p were elegible. Most of the patients were male (83%). Type of surgery: 23% pneumonectomy, and 77% lobectomy or bilobectomy. Fifty-three per cent had low BRCA1 l, 33,7% intermediate l, and 13,3% expressed high l. Most of the tumors with adenocarcinoma histology had low l (71%). With a median follow-up of 41.6 months (m), median TTP for the whole group was 22.9 m (13.4-32.5): 20.3 m for low l, 56.5 m for intermediate l, and 51.9 m for high l (P=0.31). Median OS for the whole group was 63.6 m (33.3-93.9): 55 m for low l, and not reached for intermediate and high l (P=0.58). Forty-three p (51.8%) are still alive. Conclusions: Selection of customized CT based on BRCA1 expression l is feasible and could increase time to relapse and survival in resected N1-N2 p. No statistical differences for survival: 55 months for gemcitabine-cisplatin, and not reached for docetaxel-cisplatin and for docetaxel as single agent. Randomized phase III SCAT trial with the addition of a non-pharmacogenomic control arm is ongoing (372 patients included).

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Abstract Details

Meeting

2012 ASCO Annual Meeting

Session Type

Poster Discussion Session

Session Title

Lung Cancer - Non-small Cell Local-regional/Small Cell/Other Thoracic Cancers

Track

Lung Cancer

Sub Track

Adjuvant Therapy

Citation

J Clin Oncol 30, 2012 (suppl; abstr 7011)

DOI

10.1200/jco.2012.30.15_suppl.7011

Abstract #

7011

Poster Bd #

3

Abstract Disclosures