Detection of EGFR-activating mutations from plasma DNA as a potent predictor of survival outcomes in FASTACT 2: A randomized phase III study on intercalated combination of erlotinib (E) and chemotherapy (C)

• Published in: Journal of clinical oncology Vol. 31; no. 15_suppl; p. 8021
• Main Authors: Mok, Tony, Wu, Yi Long, Lee, Jin Soo, Yu, Chong-Jen, Sriuranpong, Virote, Wen, Wei, Tsai, Julie, Truman, Matt, Klughammer, Barbara, Wu, Lin
• Format: Journal Article
• Language: English
• Published: 20-05-2013
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/jco.2013.31.15_suppl.8021

Abstract only
8021
Background: Biomarker analysis of tumor from FASTACT 2 confirmed predictive power of EGFR mut on the benefit of intercalated combination of E and C as 1st line in advanced NSCLC (T. Mok, ESMO 2012). However, only limited tumor were available. Recent development allowed us to detect EGFR mut in cell-free DNA from plasma (pEGFRmut). In this study, we studied the concordance between pEGFRmut and EGFR mut in tumor (tEGFRmut), and the role of pEGFRmut as predictor of PFS and OS. Methods: Retrospective EGFR mut testing of FFPET and plasma from FASTACT 2 were performed with two allele-specific PCR assays, cobas EGFR_FFPET test and cobas EGFR_blood test (in development). Both tests are designed to detect EGFR activating mut (exon 19 deletions, L858R, G719X). One FFPET section was used for tissue test and 2-ml plasma was used for blood test. Results: Among 268 tumors from 451 enrolled pts, 90% (241/268) were analyzable. 40% (96/241) harbored at least one activating EGFR mut. All 427 plasmas from 451 enrolled pts were analyzable. 32% (136/427) were positive for EGFR activating mut. The concordance of two tests from 224 matched tissue and plasma samples was summarized below. Using tissue as comparator, the sensitivity of plasma test was 76% (68/89) and the specificity of plasma test was 96% (130/135) respectively. Positive and negative predictive values for EGFR activating mut were 93% (68/73) and 86% (130/151) respectively. Median PFS of patients with pEGFRmut treated with intercalated combination versus chemotherapy alone was 13.8 vs. 6.1 m (HR=0.21 p<0.0001), and for pEGFR wild-type, 6.7 vs. 6.0 m (HR=0.80, p=0.06). Median OS of patients with pEGFRmut treated with intercalated combination versus chemotherapy alone was 32.4 vs. 19.0 m (HR=0.51, p=0.0035), and for pEGFR wild-type, 16.1 vs 13.3 m (HR=0.89, p=0.39). Conclusions: cobas EGFR_blood test can be used to reliably detect EGFR mutations in plasma. pEGFRmut is a potent predictor of survival outcomes in FASTACT 2. Clinical trial information: NCT00883779/ MO22201/CTONG0902. [Table: see text]