Keywords: Liquid Biospy, Bridging Study, Hazard Ratio, Tissue samples, NSCLC
Blood samples from cancer patients are also referred to as ‘liquid biopsy’ samples as opposed to the tumor samples which are obtained by ‘surgical biopsy’. To demonstrate the clinical utility of the cobas® EGFR mutation test for selecting patients for treatment with Tarceva® in blood samples, a prospectively planned, retrospective bridging analysis was conducted on the ENSURE study, a multicenter, open label, randomized Phase III study to evaluate the efficacy of Tarceva® versus chemotherapy as the first-line treatment for stage IIIB/IV NSCLC patients with EGFR mutations exon 19 deletion or L858R mutations in their tumor tissue samples. Due to the differences between the specimen types (tissue vs. plasma), patients with a positive result in a tissue sample may not yet show a positive result in a plasma sample. The test is therefore intended to initially screen patients with metastatic NSCLC for EGFR mutations in blood samples. Those patients with absence of exon 19 deletion and/or an L858R mutation in their blood samples should then have their EGFR status determined from their tissue samples. The drug efficacy of Tarceva®, based on the cobas EGFR Mutation Test in plasma, was evaluated by bridging to the drug efficacy based on the cobas EGFR Mutation Test in tissue samples in the ENSURE study. The hazard ratio for progression free survival (PFS) in patients with positive results in both plasma and tissue samples was 0.29 with a 95% CI of (0.19, 45). The hazard ratio was similar to the PFS benefit observed in the overall population (HR =0.33; 95% CI: 0.23, 0.47).
Due to the lack of sufficient volume of clinical specimens from lung cancer patients, some of the analytical performance studies used contrived samples, which consisted of sheared cell line DNA diluted into healthy donor plasma. A commutability study was conducted to demonstrate comparable performance of sheared cell line DNA diluted in healthy donor plasma as compared to the NSCLC EDTA plasma.