P2.03b-037 Prognostic Impact of 1st-Line Treatment and Molecular Testing in Advanced NSCLC in France - Results of the IFCT-PREDICT.amm Study: Topic: Biomarkers

Abstract

In 2013, recommendations for 1st line treatment in advanced NSCLC included a platinum based chemotherapy (pCT) with or without bevacizumab (BEV-pCT), an EGFR-TKI, or a non-platinum based CT (non-pCT) depending on clinical, pathological and molecular characteristics. Molecular testing for KRAS, EGFR and ALK, is routinely performed in France for advanced non-squamous NSCLC. However, the prognostic impact of the molecular status knowledge before beginning 1st line treatment is unknown. After a cross-validation study, KRAS, EGFR and ALK molecular status were assessed in 843 consecutive patients (pts) with previously untreated advanced NSCLC (all histologic subtypes) and categorized as: EGFR/ALK+, KRAS+, wild-type (WT), undetermined (UD) and not done (ND). Treatments from the 1st to 3rd line were separated into 4 groups: p-CT, BEVA-pCT, EGFR/ALK TKI and non-pCT. Demographic, clinical and pathological characteristics were collected and pts were followed-up until death. Overall survival (OS) and progression-free survival (PFS) for each line were determined. Prognostic factors including treatment categories (p-CT as reference) and biomarkers status (WT as reference) were studied by Cox model. Treatments were analyzed in 767 (91.0%) of the 843 pts enrolled between 01/2013 and 02/2014. Pts were 93.1% Caucasians, 66.2% males. Median age was 62.4 yr (28-92). 13.4% were never smokers. PS ≥2 were 21.4% and 90.3% were stage IV. 76.5% had adenocarcinoma, 14.5% squamous cell carcinoma and 9% others with WT=40.4%, KRAS+=23.1%, EGFR/ALK+=10.2%, UD=5.1%, ND=21.2%. 1st line treatments were: p-CT=75.9%, BEVA-pCT=14.2%, EGFR/ALK TKI=7.8% and non-pCT=2.1%. With a 30.3 months (mo) median of follow-up, median OS and PFS were 10.7 mo and 5.3 mo, respectively. Factors independently associated with shorter OS were PS≥2 (HR=2.08, p<.0001), KRAS+, UD and ND mutation status (HR=1.40, p=.002; 1.53, p=.02; 1.29, p=.02), and non-pCT as 1st line treatment (HR=1.92, p=.01), while EGFR/ALK+ (HR=.38, p<.0001) and BEVA-pCT (HR=.54, p<.001) were associated with better survival. There was no interaction effect between biomarkers status and OS treatment groups. However, BEVA-pCT in 1st line therapy in KRAS+ and WT NSCLC (p<.0001 and <.0003, respectively) was associated with longer survival compared to p-CT, while giving a TKI or p-CT in 1st line therapy in EGFR/ALK+ NSCLC did not affect OS. Results from the IFCT-PREDICT.amm study suggest that prognosis of advanced NSCLC might be optimized in 1st line setting by the knowledge of EGFR/ALK molecular status and the opportunity to give a BEVA-pCT regimen, especially in patients with KRAS+ and WT tumor.