Serum and tumor biomarkers to predict outcome in the eLung trial, a multicenter, randomized phase IIb study of standard platinum doublets (PD) plus cetuximab (CET) as first-line treatment of advanced non-small cell lung cancer (NSCLC).

Abstract

8044 Background: The eLung trial randomized chemotherapy naïve advanced NSCLC patients (pts) to 1 of 3 PD and concurrent CET followed by CET maintenance until progression, stratified by non-squamous (NSQ) and squamous (SQ) histology. Primary outcome results were reported (ESMO, Schwartzberg 2012). Pre-treatment tumor tissue and serum samples were prospectively collected. Methods: Tumor samples were analyzed for H-score (graded 0-300), calculated by the intensity and number of cells expressing EGFR by IHC; a score of >200 was considered high (Pirker 2011). Mutation analysis of EGFR and KRAS was performed by PCR. The VeriStrat multivariate serum protein test was performed on available serum samples assigning good and poor classifications (Taguchi 2007). Results: Of 601 pts enrolled on the trial, 378 consented to blood/tissue or both. The available tissue (N=210) and serum subsets (N=203) had similar demographics and survival outcome to the full trial set. Results for biomarkers/cohorts in the Table demonstrate that VeriStrat was highly significant for OS in all pts and NSQ, while H-score and EGFR mutations were significant only in NSQ. In adjusted Cox analysis VeriStrat was an independent predictor for OS, HR=.665, p=.026; H-score was not. Conclusions: VeriStrat classification significantly correlated with survival outcome in all pts treated with PD and CET and the NSQ subset; tissue biomarkers correlated in NSQ only. Further evaluation of these markers is warranted. [Table: see text]

Prognostic role of the VeriStrat test in first line patients with non-small cell lung cancer treated with platinum-based chemotherapy

“…In the eLung trial, chemotherapy-naïve advanced NSCLC patients were randomized to one of three regimens of platinum doublets: carboplatin (AUC 6, day 1) plus paclitaxel (200 mg/m 2, day 1), or carboplatin (AUC 6, day 1) or cisplatin (75 mg/m 2 ) plus gemcitabine (1000 mg/m 2 , days 1 and 8), or carboplatin (AUC 6, day 1) or cisplatin (75 mg/m 2 ) plus pemetrexed (500 mg/m 2 , in non-squamous patients) and concurrent cetuximab (loading dose 400 mg/m 2 , followed by 250 mg/m 2 ), q 21 days, administered for four to six cycles, followed by cetuximab maintenance (500 mg/m 2 ) q 2 weeks; 206 out of 601 of these patients had serum available for testing; 203 received VeriStrat classification. The results for the combined arms were presented at the ASCO congress, 2013 [27].…”

“…In this paper we examine the results of three recently reported studies where VeriStrat was applied to samples from advanced NSCLC patients treated with platinum-based chemotherapy in the front line [26][27][28]. These studies included well-characterized populations of patients recruited in the scope of clinical trials, which were treated with platinum-based chemotherapy, reflecting common clinical practice.…”