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

7500 Background: IFCT-0002 phase 3 trial compared two timings of CT in early lung cancer, all before surgery (PRE) versus PERIoperative, and two CT regimens, CDDP-Gem vs. CBDCA-Pac. 528 patients were randomized. Early results showed no difference between the two CT regimens for response rate or tolerance, but a better compliance in PRE vs. PERI arm. We hypothesized that molecular markers could help to define the subgroups that did not beneficiate from CT. Methods: Molecular alterations in key pathways regulating G1/S transition or apoptosis were screened. TP53, EGFR and K-RAS mutations, RASSF1A, DAPK, ECAD, FHIT, TIMP3 and p16 promoter gene methylation, 3p, 17p and 9p LOH were evaluated in 178 patients with snap-frozen tissue collected at time of surgery. Results: K-ras mutations identified in 16.3% of patients, was the only molecular alteration associated with the absence of tumor response to chemotherapy (crude RR = 2.13 95%CI [1.11–4.55], p=0.019). However, K-ras mutations were not associated with PFS ...