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Evolution and clinical impact of EGFR mutations in circulating free DNA in the BELIEF trial


Abstract

BACKGROUND

Longitudinal evaluation of mutations in blood samples was a pre-specified secondary objective in the BELIEF trial of erlotinib/bevacizumab in advanced EGFR-positive NSCLC. Here we report the testing results and explore the correlation of EGFR status in blood with clinical outcomes.

METHODS

Blood samples were prospectively collected from patients at baseline, response evaluation and progression and sent to a central laboratory. Circulating free DNA (cfDNA) was purified and EGFR mutations were analyzed with a validated real-time quantitative PCR assay.

RESULTS

EGFR exon-19/21 mutations were detected in 55/91 (60.4%) baseline blood samples and correlated with a significantly worse PFS: 11.4m (95%CI:9.0-14.8m) for the positive patients vs. 22.9m (95%CI:9.5-33.9m) for the negatives, (log-rank.p=0.0020). Among the 74 samples at response, exon-19/21 mutations were detected only in three cases (4.1%). In contrast, 29/58 patients (50.0%) were exon 19/21 positive at progression and showed a significantly worse median OS of 21.7m (95%CI:17.0-30.9m), compared to 37.4m (95%CI:22.6-53.1m) for negatives (log-rank.p=0.011). Blood samples at the three timepoints were available for 48 patients. Of those, among 14 exon-19/21 EGFR-negative at presentation, 13 (93%) were persistently negative for the sensitizing mutations after progression and the p.T790M could only be detected in the blood of two.

CONCLUSIONS

Longitudinal testing of EGFR mutations in blood can offer valuable clinical information. In patients of the BELIEF study, detection of EGFR mutations in cfDNA at presentation was associated with shorter PFS, while positivity at progression correlated with shorter OS. Finally, patients negative in blood at presentation were almost invariably negative at relapse.

Abstract

BACKGROUND

Longitudinal evaluation of mutations in blood samples was a pre-specified secondary objective in the BELIEF trial of erlotinib/bevacizumab in advanced EGFR-positive NSCLC. Here we report the testing results and explore the correlation of EGFR status in blood with clinical outcomes.

METHODS

Blood samples were prospectively collected from patients at baseline, response evaluation and progression and sent to a central laboratory. Circulating free DNA (cfDNA) was purified and EGFR mutations were analyzed with a validated real-time quantitative PCR assay.

RESULTS

EGFR exon-19/21 mutations were detected in 55/91 (60.4%) baseline blood samples and correlated with a significantly worse PFS: 11.4m (95%CI:9.0-14.8m) for the positive patients vs. 22.9m (95%CI:9.5-33.9m) for the negatives, (log-rank.p=0.0020). Among the 74 samples at response, exon-19/21 mutations were detected only in three cases (4.1%). In contrast, 29/58 patients (50.0%) were exon 19/21 positive at progression and showed a significantly worse median OS of 21.7m (95%CI:17.0-30.9m), compared to 37.4m (95%CI:22.6-53.1m) for negatives (log-rank.p=0.011). Blood samples at the three timepoints were available for 48 patients. Of those, among 14 exon-19/21 EGFR-negative at presentation, 13 (93%) were persistently negative for the sensitizing mutations after progression and the p.T790M could only be detected in the blood of two.

CONCLUSIONS

Longitudinal testing of EGFR mutations in blood can offer valuable clinical information. In patients of the BELIEF study, detection of EGFR mutations in cfDNA at presentation was associated with shorter PFS, while positivity at progression correlated with shorter OS. Finally, patients negative in blood at presentation were almost invariably negative at relapse.

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Additional indexing

Contributors:European Thoracic Oncology Platform (ETOP) BELIEF trial
Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Oncology and Hematology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:1 March 2020
Deposited On:21 Jan 2020 13:23
Last Modified:22 Feb 2020 02:05
Publisher:Elsevier
ISSN:1556-0864
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.jtho.2019.11.023
PubMed ID:31812754

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