NEJ026: Final overall survival analysis of bevacizumab plus erlotinib treatment for NSCLC patients harboring activating EGFR-mutations.

Abstract

9506 Background: In NEJ026, a phase III trial comparing bevacizumab plus erlotinib (BE) to erlotinib monotherapy (E) for EGFR-mutated non-small-cell lung cancer (NSCLC), we demonstrated the progression-free survival (PFS) of BE was significantly superior to E (Saito et al. Lancet Oncol. 2019 May;20(5):625-635.). However overall survival analysis were immature at the cutoff date. Methods: Chemotherapy-naïve pts with advanced non-squamous NSCLC harboring EGFR-mutation were randomly assigned to receive either combination with erlotinib (150 mg daily) plus bevacizumab (15 mg/kg iv q3w) or erlotinib (150 mg daily). The primary endpoint was PFS. Secondary endpoints were OS, RR, safety, and QoL. Results: The 226 pts were assigned to BE (n=112) and E (n=114). For the follow-up OS analysis, the data cut-off date was 30 November 2019. Median follow up time was 39.2 months. Median OS was 50.7 months (95% CI, 37.3 months to not reached) with BE and 46.2 months (95% CI, 38.2 months to not reached) with E (hazard ratio, 1.00; 95% CI, 0.68 to 1.48). Twenty-nine patients (25.9%) in BE and twenty-six patients (23.2%) in E were treated by osimertinib as second line treatment. The median survival time between enrollment and progressive disease of second-line treatment (median PFS2) was 28.6 months (95% CI, 22.1 months to 35.9) with BE and 24.3 months (95% CI, 20.4 months to 29.1 months) with E (hazard ratio, 0.80; 95% CI, 0.59 to 1.10). In both arms, the median OS of patients with osimertinib second-line treatment were longer than other second-line chemotherapy groups [50.7 months (95% CI, 38.0 months to 50.7 months) vs 40.1 months (95% CI, 29.5 months to not reached), (hazard ratio, 0.645; 95% CI, 0.40 to 1.03), respectively. Conclusion: The additional effect of bevacizumab on erlotinib monotherapy for NSCLC with EGFR mutations gradually decreased in the order of PFS2 and survival, with no significant differences. Clinical trial information: UMIN000017069 .

Role of Antiangiogenic Agents Combined With EGFR Tyrosine Kinase Inhibitors in Treatment-naive Lung Cancer: A Meta-Analysis

“…Considering that the updated PFS and OS data from the NEJ026 study were consistent with our analysis, we believe these data would have had limited effects on the conclusions of our meta-analysis. 39 EGFR and VEGF signaling pathways are independent but closely interrelated because they share the Ras/Raf/MEK signal transduction pathway. 40 EGFR activation mainly leads to tumor cell survival, proliferation, angiogenesis, and metastasis.…”

Dual EGFR-VEGF Pathway Inhibition: A Promising Strategy for Patients With EGFR-Mutant NSCLC

“…49 The PFS for patients in the erlotinib plus bevacizumab group was significantly increased compared with patients who received erlotinib alone (16.9 versus 13.3 mo, HR: 0.605, p ¼ 0.016). 50 The phase 3 ARTemis (CTONG 1509) trial compared erlotinib plus bevacizumab versus erlotinib in 311 treatment-naive Chinese patients with advanced EGFR-mutant NSCLC. PFS was significantly improved with the addition of bevacizumab to erlotinib (18 versus 11.2 mo, HR: 0.55, p < 0.001).…”

“…48 In the larger phase 3 NEJ026 study (n ¼ 226), the median OS was 50.7 months (bevacizumab þ erlotinib) versus 46.2 months (erlotinib)-again, exhibiting no difference (HR: 1.007, p ¼ 0.97). 50 To date, no OS data is available for the ARTemis study, and we are awaiting the OS data to mature in the even larger RELAY trial (n ¼ 449).…”

<p>Anti-Angiogenic Therapy in the Treatment of Non-Small Cell Lung Cancer</p>

“…It is reported that the PFS is significantly prolonged in the EB group (median 16.9 months vs 13.3 months, HR=0.605, 95% CI 0.417 to 0.877, P=0.016); however, EB provided no further benefit to the OS of the patients (median 50.7 months vs 46.2 months, HR=1.007, 95% CI 0.681 to 1.490, P=0.973). 95 , 96 In 2017, Wang et al conducted a phase III study, which evaluated the efficacy and safety of EB + panitumumab in patients with stage II–IV NSCLC. The OS (median 10.4 months vs 8.9 months, P=0.003) and PFS (median 4.6 months vs 1.9 months, P=0.031) are significantly prolonged in the combination group compared with erlotinib alone.…”