Dataset Information

Evaluation of plasma EGFR mutation as an early predictor of response of erlotinib plus bevacizumab treatment in the NEJ026 study.

ABSTRACT: BACKGROUND:The NEJ026 Phase 3 study demonstrated that erlotinib and bevacizumab (BE)-treated NSCLC patients with EGFR mutations had significantly better progression-free survival (PFS) than those treated with erlotinib alone (E). This study included a prospective analysis of the relationship between the mutational status of EGFR in plasma circulating tumor DNA (ctDNA) and the efficacy of TKI monotherapy or combination therapy. We describe these results herein. METHODS:Plasma samples were collected from patients enrolled in NEJ026 at the start of treatment (P0), 6 weeks after the start of treatment (P1), and upon confirmation of progressive disease (P2). Plasma ctDNA was analyzed using a modified PNA-LNA PCR clamp method. PFS and OS according to EGFR status at the time of plasma collection were evaluated. FINDINGS:Plasma activating EGFR mutation (aEGFR) at P0 was detected in 68% of cases; patients without plasma aEGFR had longer PFS. The frequency of T790M mutation at P2 was similar in both arms: 8 (19.0%) in BE and 11 (20.8%) in E. Based on the aEGFR profiles, PFS was evaluated among three groups: type A [P0(-), P1(-)], type B [P0(+), P1(-)], and type C [P0(+), P1(+)]. This revealed that BE was more efficacious than E, and that BE was associated with improved PFS in all types. INTERPRETATION:Pre-treatment plasma aEGFR status have a potential of early predictor of response of TKI efficacy. Monitoring plasma aEGFR mutation will contribute to selection and continuation of treatment with BE or E. FUNDING:Chugai Pharmaceutical.

SUBMITTER: Fukuhara T

PROVIDER: S-EPMC7334809 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Evaluation of plasma EGFR mutation as an early predictor of response of erlotinib plus bevacizumab treatment in the NEJ026 study.

Fukuhara Tatsuro T Saito Haruhiro H Furuya Naoki N Watanabe Kana K Sugawara Shunichi S Iwasawa Shunichiro S Tsunezuka Yoshio Y Yamaguchi Ou O Okada Prof Morihito PM Yoshimori Kozo K Nakachi Ichiro I Gemma Prof Akihiko PA Azuma Koichi K Kurimoto Futoshi F Tsubata Yukari Y Fujita Yuka Y Nagashima Hiromi H Asai Gyo G Watanabe Satoshi S Miyazaki Masaki M Hagiwara Prof Koichi PK Nukiwa Prof Toshihiro PT Morita Prof Satoshi PS Kobayashi Prof Kunihiko PK Maemondo Prof Makoto PM

EBioMedicine 20200703

<h4>Background</h4>The NEJ026 Phase 3 study demonstrated that erlotinib and bevacizumab (BE)-treated NSCLC patients with EGFR mutations had significantly better progression-free survival (PFS) than those treated with erlotinib alone (E). This study included a prospective analysis of the relationship between the mutational status of EGFR in plasma circulating tumor DNA (ctDNA) and the efficacy of TKI monotherapy or combination therapy. We describe these results herein.<h4>Methods</h4>Plasma sampl ...[more]

PMID: 32629391

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Project description:Importance:Erlotinib is a standard first-line therapy for patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Median progression-free survival (PFS) with erlotinib is approximately 10 months. Objective:To determine whether adding bevacizumab to erlotinib treatment results in superior progression-free survival compared with erlotinib alone. Design, Setting, and Participants:This phase 2 randomized clinical trial compared erlotinib plus bevacizumab with erlotinib alone in EGFR-mutant NSCLC. The trial was conducted in 17 US academic and community medical centers among 88 patients with EGFR exon 19 deletion or exon 21 L858R mutation based on local testing and stage 4 NSCLC who were eligible for bevacizumab. Patients were enrolled between November 2, 2012, and August 22, 2016, and followed up for a median (range) of 33 (0.7-62.5) months. Data were analyzed on August 28, 2018, and included data from November 2, 2012, to August 20, 2018. Interventions:Patients were randomized with equal allocation to 150 mg of oral erlotinib daily alone or with 15 mg/kg of intravenous bevacizumab every 3 weeks. Study therapy continued until disease progression, unacceptable adverse event, or withdrawal of consent. Main Outcomes and Measures:The primary outcome was PFS as assessed by the investigator; secondary outcomes were objective response rate (ORR), adverse events, and overall survival (OS). Analysis was designed to detect a hazard ratio (HR) of 0.667 for PFS (an improvement from a median PFS of 10 to 15 months). Results:Among 88 patients enrolled, the median (range) age was 63 (31-84) years; 62 patients (70%) were female; 75 (85%) were white, 8 (9%) were African American, 3 (3%) were Asian, and for 2 (2%), data on race were not available. Forty-eight patients (55%) were never smokers, 45 patients (51%) were of Eastern Cooperative Oncology Group performance status 1, and 59 patients (67%) had EGFR exon 19 deletion. Compared with erlotinib, the combination did not result in a significant difference in PFS (HR,?0.81; 95% CI, 0.50-1.31; P?=?.39; median PFS 17.9 [combination] and 13.5 months [erlotinib]), ORR (81% vs 83%; P?=?.81), and OS (HR,?1.41; 95% CI, 0.71-2.81; P?=?.33; median OS, 32.4 months [combination] and 50.6 months [erlotinib]). Adverse events of grade 3 or higher observed in 5 or more patients in the combination and erlotinib arms were skin eruption in 11 (26%) vs 7 (16%) patients, diarrhea in 4 (9%) vs 6 (13%) patients, hypertension in 17 (40%) vs 9 (20%) patients, and proteinuria in 5 (12%) vs 0 (0%) patients. Conclusions and Relevance:Erlotinib plus bevacizumab compared with erlotinib did not result in a significant improvement in PFS in EGFR-mutant NSCLC. Trial Registration:ClinicalTrials.gov identifier: NCT01532089.

Dataset Information

Evaluation of plasma EGFR mutation as an early predictor of response of erlotinib plus bevacizumab treatment in the NEJ026 study.

Publications

Evaluation of plasma EGFR mutation as an early predictor of response of erlotinib plus bevacizumab treatment in the NEJ026 study.

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