Association between different potential predictive markers from TRUST, a trial of erlotinib in non-small cell lung cancer (NSCLC)

Abstract

7651 Background: Recent studies have examined potential predictive markers in NSCLC patients (pts) treated with EGFR tyrosine kinase inhibitors. However, few data are available on inter-relationships between different markers. Clinical and molecular markers were analyzed for patients from TRUST, an open label, non-randomized trial initiated to provide erlotinib access to pts with advanced NSCLC. Methods: 393 German pts (99% Caucasian) with stage IIIb/IV NSCLC were included. Markers/characteristics assessed were: EGFR (282 pts) and phosphorylated MAPK (pMAPK; 109 pts) using immunohistochemistry (IHC; positive status was defined as: ≥10% of tumor cells with any membrane staining for EGFR; and H-score ≥200 for pMAPK), EGFR gene copy number (135 pts) using fluorescence in-situ hybridization (FISH), EGFR mutations (86 pts), KRAS mutations (108 pts), tumor type (281 pts), smoking status (392 pts) and gender (393 pts). Results: EGFR FISH+ pts were likely to also be EGFR IHC+: 92.9% (26/28) of EGFR FISH+ pts were EGFR IHC+, and 92.6% of EGFR IHC- pts were also EGFR FISH- (p<0.1). pMAPK expression status was not related to other markers. 15.7% (17/108) pts had KRAS and 7.0% (6/86) had EGFR mutations; no pts had mutations in both genes, indicating that these mutations might be mutually exclusive. Both KRAS mutations and histology were associated with smoking status. 94.1% (16/17) pts with KRAS mutations and 91.6% (87/95) pts with squamous-cell carcinoma were smokers. In female pts, the occurrence of adenocarcinoma was significantly higher (73.6% vs 55.4% in males; p<0.001), possibly influenced by a lower incidence of smokers in this group (51.3% vs 92.2% in males; p<0.001). Conclusions: The availability of a large number of tumor samples from the TRUST study, and assessment of a broad range of markers allows investigation of relationships between various tumor/patient characteristics. Understanding these complex inter-relationships may shed light on the role of each marker. Specific combinations of markers may prove useful in predicting clinical benefit from erlotinib. As the study is ongoing, additional data will be available and presented. No significant financial relationships to disclose.

The impact of both platinum-based chemotherapy and EGFR-TKIs on overall survival of patients with advanced non-small cell lung cancer

“…After EGFR-TKIs were approved for advanced NSCLC, the OS of advanced NSCLC patients increased [9] . In the BR.21 [12] and TRUST [13] studies, erlotinib monotherapy had better efficacy and was safer in second-line or third-line treatment than placebo. Recently, the Tailor study indicated that patients with wild-type EGFR who underwent previous treatment did not obtain a PFS benefit from second-line erlotinib compared with docetaxel [14] .…”