CHICAGO―Serum proteomic VeriStrat classification test status predicts which patients will see overall survival (OS) benefits from second-line chemotherapy instead of erlotinib therapy for advanced non-small cell lung cancer (NSCLC), after progression on platinum-based treatment regimens, report authors of a proteomic-stratified phase 3 Italian study presented at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting.

“Our results indicate that in NSCLC, patients classified as VeriStrat Poor have better survival with chemotherapy than erlotinib and patients classified as VeriStrat Good have similar survival with erlotinib and chemotherapy,” said coauthor Vanesa Gregorc, MD, of the San Raffaele Scientific Institute in Milan, Italy, who presented the group’s findings.

Prior studies have shown that “EGFR-TKIs [epidermal growth factor receptor tyrosine kinase inhibitors] are more effective in NSCLC patients with EGFR activating mutations,”

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In order to evaluate the predictive utility of VeriStrat classifications on NSCLC survival outcomes associated with second-line erlotinib versus chemotherapy, the coauthors enrolled a total of 285 patients with cytological or histological diagnoses of NSCLC at advanced stages (IIIB-IV), one previous platinum-based therapy, and an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0- 2, of whom 263 were included for analysis. (Of the patients excluded from analysis, 19 never received therapy and three experienced “major protocol violations,” the coauthors noted.)

Patients and coauthors were blinded to VeriStrat status. Based on VeriStrat test outcomes, patients were classified as VeriStrat Good or VeriStrat Poor, and each group was randomly assigned 1:1 to receive either erlotinib (150 mg daily; n=134) or chemotherapy (pemetrexed 500 mg/m2 or docetaxel 75 mg/m2; n=129). The chemotherapy group had 88 (68%) patients categorized as VeriStrat Good, and 41 (32%) as VeriStrat Poor; the erlotinib group had 96 (72%) VeriStrat Good participants and 38 (28%) VeriStrat Poor, Dr. Gregorc said.

Patients in both sets of treatment groups were stratified by ECOG-PS and smoking status. Crossover was permitted upon disease progression.

Median overall survival (OS) was 9 months from randomization (6.8-10.9 months) among patients in the chemotherapy group and 7.7 months (5.9-10.4) for erlotinib (hazard ratio [HR], 1.14; 95% CI: 0.88-1.49; P=0.313), Gregorc reported. But when VeriStrat Poor patients who received chemotherapy were compared with those who received erlotinib, chemotherapy was associated with significantly better OS (median OS, 6.3 vs. 2.98 months; HR, 1.72; 95% CI: 1.00-2.74; P=0.02), Dr. Gregorc reported.

Subgroup analyses showed that ECOG-PS and VeriStrat classification each was prognostic of outcome, independent of treatment, she said. Smoking history, histology (squamous vs. nonsquamous) gender and age did not significantly predict survival in multivariate analysis, in contrast.

“VeriStrat is predictive of significant differential treatment benefit between chemotherapy and erlotinib when adjusted for potential confounding factors,” Dr. Gregorc explained.

Analysis of outcomes among VeriStrat Poor patients with EGFR wildtype or unknown status strengthened VeriStrat classification’s predictiveness of OS outcome, she noted (HR, 1.94; 95% CI: 1.09-3.43; P=0.2).

“PROSE is the first completed prospective, biomarker-stratified validation study in oncology to test treatment/biomarker interaction,” Dr. Gregorc said. “Serum proteomic VeriStrat classification is clinically useful to guide treatment decisions in NSCLC patients with unknown or wildtype EGFR status, in a second-line setting.”