Randomized Phase III Trial of Customized Adjuvant Chemotherapy (CT) According BRCA-1 Expression Levels in Patients with Node Positive Resected Non-Small Cell Lung Cancer (NSCLS) SCAT: A Spanish Lung Cancer Group Trial (Eudract:2007-000067-15; NCTgov: 00478699).

7507 Background: Postop platinum-based CT improves outcomes in resected NSCLC with N+ (St II-IIIA). Analysis of expression of genes involved in DNA repair could be used to individualize optimal CT. BRCA1 may act as a differential regulator of response to cisplatin (Cis) and antimicrotubule agents. Methods: Phase III multicenter trial. After surgery, patients (p) with St II and III were random 1:3 to control arm (Cis-Docetaxel) or to experimental arm with treatm. according BRCA1 express. levels (low : Cis-Gemcitabine; intermediate : Cis-Doc; high: Doc alone). Stratification factors: N1 vs N2; age < or > 65 y; non-squamous vs squamous (Sq) ; lobectomy vs pneumonectomy). Planned PORT in N2. Primary end-point OS. Secondary: DFS, toxicity, compliance, recurrence pattern. Statistical hypothesis: 20% increase 5y surv. control group (45%). Results: From June 2007 to May 2013, 591 p were screened and 500 of them were random: 108 in control, 392 experimental (110 p Cis-Gem, 127 Cis-Doc and 110 Doc alone). No disbalance between arm for prognostic factors: Median age 64 y; 79% males, 21% females; 43% Sq, 49% Adeno; pneumonectomy 26%; N1 58%, N2 48%; smoking habit: 57% former, 32% current, 11% never. Median tumor size 4.4 cm (0.8-15.5). Median mRNA BRCA1 levels 15.78 (0.73-132). Mean BRCA1 levels 6.95 Adeno vs 20.29 Sq (p < 0.001). Median f-u 30 months (0-79 m). With a cut-off of March 15th median survival has not reached both arms and no significant diffs. have been seen for OS with HR 0.866 (p = 0.45) or DFS (HR 1). In exper. group HR for OS was 0.842 (NS) comparing low with high-BRCA1 levels. In p with high-BRCA1 levels control treatm. (Cis-Doc) was superior to exper. (Doc) with HR 1.24 (NS). For p receiving all planned treatm. HR is 0.63 with p = 0.043 compared with p not able to complete treatm. P with Sq histology showed a longer DFS (HR 0.73; p = 0.05) but without diff. in OR (HR 1). Conclusions: BRCA1 based adjuvant CT does not improve OS. In p with high-BRCA1 levels Doc alone is inferior to Cis-Doc. Full dose of planned treatm. confers a survival advantage, however, longer follow-up is still warranted. Clinical trial information: 00478699.