Spanish customized adjuvant trial (SCAT) based on BRCA1 mRNA levels
2008; Lippincott Williams & Wilkins; Volume: 26; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2008.26.15_suppl.7533
ISSN1527-7755
AutoresM. Cobo, Bartomeu Massutí, Teresa Morán, Iman Chaib, Laia Perez‐Roca, Ulpiano Jiménez, David Aguiar Bujanda, J.L. González-Larriba, Joanne Michelle D. Gomez, R. Rosell,
Tópico(s)BRCA gene mutations in cancer
Resumo7533 Background: Patients (p) with low BRCA1 mRNA levels attained longer survival when treated with cisplatin-based chemotherapy (Taron et al. 2004), while p with high BRCA1 levels attained longer survival when treated with taxanes-based therapy (Quinn et al. 2007). Early NSCLC p whose tumors had high BRCA1 levels had significantly worse survival (Rosell et al. 2007). Upregulated BRCA1 is part of a characteristic gene signature in aggressive lung cancers (Deeb et al. 2007). Methods: Adjuvant chemotherapy was customized based on BRCA1 mRNA levels in 84/100 completely resected N1 and N2 NSCLC p. 11 p with high BRCA1 levels received docetaxel (doc); 29 p with intermediate BRCA1 levels received doc/cisplatin (cis); 44 p with low BRCA1 levels received cis/gemcitabine (gem). Results: Median survival has not been reached in p with high or intermediate BRCA1 levels, while it is 25.6 months (m) in p with low levels (P=0.04). In a multivariate analysis for survival in all 84 p, the hazard ratios (HR) were 5.23 for p with high BRCA1 levels (P=0.07), 3.57 for p with tumor size > 4 cm (P=0.07). In the multivariate analysis of 42 N2 p, the HRs were 0.13 for 18 p receiving postoperative radiotherapy (P=0.04) and 22 for 15 p with intermediate or high BRCA1 levels (P=0.01). Conclusions: Interim analyses show that single-agent doc has no detrimental effect on survival in comparison with doc/cis. In addition, high BRCA1 mRNA expression could be a poor prognostic marker. The Spanish Lung Cancer Group has opened a phase III study of customized adjuvant chemotherapy based on BRCA1 mRNA levels. N2 p HR (95% CI) p Post-operative radiotherapy Yes 18 0.12 (0.02–0.89) 0.04 No 24 1 BRCA1 mRNA levels Low 24 1 Intermediate/High 15 22.43 (2.02–248.62) 0.01 Tumor size ≤ 4 24 1 > 4 18 1.63 (0.34- 7.91) 0.54 No significant financial relationships to disclose.
Referência(s)