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.

Real-World Characteristics and Outcomes of Advanced Non-Small-Cell Lung Cancer Patients with EGFR Exon 19 Deletions or Exon 21 Mutations

“…One meta-analysis of 12 studies comparing EGFR-TKI monotherapy with chemotherapy concluded that patients with NSCLC and ex19del mutations had better progression-free survival (PFS; hazard ratio [HR]: 0.69; 95% CI: 0.57-0.82; p < 0.001) and overall survival (OS; HR: 0.61; 95% CI: 0.43-0.86; p = 0.005) than patients who had Leu858Arg mutations [9]. However, this analysis did not include the more recent Phase III trials: ARCHER 1050 (dacomitinib vs gefitinib), FLAURA (osimertinib vs gefitinib or erlotinib), NEJ026 (erlotinib plus bevacizumab) or RELAY (erlotinib plus ramucirumab) [10][11][12][13]. Other meta-analyses that compared monotherapy with erlotinib to combination therapy with erlotinib plus bevacizumab or ramucirumab concluded Table 1.…”

Rational Application of First-Line EGFR-TKIs Combined with Antiangiogenic Inhibitors in Advanced EGFR-Mutant Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis

“…In the NEJ026 study, results of the polymerase chain reaction clamp-based detection test in tissue/blood after drug resistance in the two groups showed that the proportion of T790M was 24% vs. 26%, respectively. The proportion of patients receiving follow-up osimertinib in the two groups was similar [ 13 , 25 ]. In the RELAY study after drug resistance, liquid biopsy samples were detected using a next-generation sequencing (NGS) method.…”

Phase II open‐label multicenter study to assess the antitumor activity of afatinib in lung cancer patients with activating epidermal growth factor receptor mutation from circulating tumor DNA: Liquid‐Lung‐A

“…In the recently published BELIEF trial, 16 activating EGFRm was detected in ctDNA in 55 of 91 (60%) patients with tumor EGFRm, and the patients with ctDNA EGFRm showed a correlation with a shorter PFS compared to ctDNA EGFRm‐negative patients. In a biomarker analysis of the NEJ026 phase III study comparing erlotinib plus bevacizumab combination therapy with erlotinib monotherapy in EGFR ‐mutated NSCLC, 17 patients without ctDNA EGFRm at baseline had longer PFS compared to patients with ctDNA EGFRm. In addition, patients who showed a negative conversion of ctDNA EGFRm from baseline to six weeks after the start of treatment had longer PFS compared with patients who had ctDNA EGFRm continuously detected after six weeks.…”