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J.L. Martin De Nicolas
ORAL 04 - Adjuvant Therapy for Early Stage Lung Cancer (ID 99)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
ORAL04.05 - Results Ph III Trial Customized Adjuvant CT after Resection of NSCLC with Lymph Node Metastases SCAT: A Spanish Lung Cancer Group Trial (ID 2983)
10:45 - 12:15 | Author(s): J.L. Martin De Nicolas
Postop platinum-based CT improves outcomes in completely resected NSCLC with nodal involvement (St II-IIIA) but compliance and outcomes remain limited. Analysis of expression of genes involved in DNA repair could be used to individualize optimal CT. BRCA1 is primarily involved in the repair of double strand DNA breaks and functions as a differential regulator of response to cisplatin (Cis) and antimicrotubule agents. BRCA1 defficiency can enhance Cis resistance. Loss of BRCA1 function is associated to sensitivity to DNA-damaging CT and may also be associated with resistance to spindle poisons
Randomized phase III multicenter trial. After surgery patients (p) with St II and III NCSLC were random 1:3 to control arm (3 cycles Cis-Docetaxel) or to experimental arm with treatment assigned according BRCA1 expression levels (low levels: Cis-Gemcitabine; intermediate levels: Cis-Doc; high levels: Docetaxel alone). Stratifification factors: N1 vs N2; age < or > 65 y; non-Squamous vs Squamous (Sq) histology; lobectomy vs pneumonectomy). Planned PORT in N2. Primary end-point OS. Secondary end-points DFS, toxicity profile (CTCAE v 3.0) /compliance, recurrence pattern. Statistical hypothesis: increase 20% 5y survival rate control group (45%)
From June/2007 to May/2013, a total of 591 p were screened and 500 of them were randomized in the study, 108 in control arm, 392 in experimental arm. In experimental arm 110 p received Cis-Gem, 127 Cis-Doc and 110 Doc alone. There were no significant differences between arm for known prognostic factors: Median age 64 y; 79% males, 21% females; 43% Sq, 49% Adenoca, 8% others; 57% former smokers, 32% current smokers, 11% never smokers; pneumonectomy 26%; N1 58%, N2 48%. Median tumor size 4.4 cm (0.8-15.5 cm). Median mRNA BRCA1 levels 15.78 (0.73-132). Mean BRCA1 levels 6.95 in Adenoca vs 20.29 in Sq (p<0.001). P with Sq histology showed a longer DFS (HR 0.73; p=0.05) but without differences in OR (HR 1) Median follow-up 28 months (0-79 m), with a cut-off of March 15[th] 2015, median survival has not reached both arms and no significant differences have been seen for OS with hazard ratio (HR) 0.866 (p=0.45) or DFS with HR 1. In experimental group HR for OS was 0.842 (NS) comparing low with high-BRCA1 levels. In p with high-BRCA1 levels control treatment (Cis-Doc) was superior to experimental (Doc) with HR 1.24 (NS).In non-Sq histology experimental treatment was superior to control with HR 0.75. For p receiving all planned treatment HR is 0.63 with p = 0.043 compared with p not able to complete treatment.
Overall survival data are still immature because median survival is not reached with a median f-u 28 m for this N+ population. At this time analysis BRCA1 based adjuvant CT does not improve overall OS. In p with high BRCA1 levels Doc alone is inferior to Cis-Doc. BRCA-1 levels are higher in Sq and in non-Sq histology a trend to better survival in experimental arm was found. Full dose of planned treatment confers a survival advantage, however, longer follow-up is still warranted.
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