Randomized Phase 2 Study of Osimertinib Plus Bevacizumab Versus Osimertinib for Untreated Patients With Nonsquamous NSCLC Harboring EGFR Mutations: WJOG9717L Study

Leptomeningeal metastasis (LM) is a lethal complication of advanced non-small cell lung cancer (NSCLC) with rapid deterioration and poor prognosis. It has no standard treatment for epidermal growth factor receptor mutation (EGFRm) NSCLC, and improving the clinical outcomes for patients with LM has become an urgent problem in clinical treatment. Both almonertinib and bevacizumab are capable of crossing the blood–brain barrier with comparable central nervous system effectiveness. To date, the almonertinib treatment in combination with bevacizumab in EGFRm NSCLC with LM has not been studied. We herein present five cases to further evaluate the effectiveness and tolerability of almonertinib in combination with bevacizumab for patients with EGFRm NSCLC and LM. For the first time, we report that almonertinib plus bevacizumab can not only effectively improve the neurological symptoms caused by LM but also prolong the survival time of patients with limited and controllable side effects, which provided a novel therapeutic approach for LM from EGFRm NSCLC.

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Section: Discussionmentioning

confidence: 99%

“…However, patients with symptomatic brain metastasis or LM were excluded from these clinical studies. As such, the therapeutic benefits of osimertinib plus bevacizumab for LM merit further investigation (18,19). Preclinical studies have confirmed that almonertinib has a higher intracranial concentration and good BBB penetration.…”

Section: Casementioning

confidence: 99%

Case report: Almonertinib in combination with bevacizumab for leptomeningeal metastases from epidermal growth factor receptor-mutation non-small cell lung cancer: Case series

Zhang

Zhang²,

Cheng³

et al. 2022

Front. Oncol.

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“…WJOG9717L which combined osimertinib with bevacizumab reported no PFS benefit compared to osimertinib alone. 99 FLAURA2 has safely opened up its investigation by demonstrating a manageable safety and tolerability in patients treated with osimertinib in combination with pemetrexed and platinum doublet chemotherapy. 100 We have previously experienced in NEJ009 trial that gefitinib in combination with chemotherapy could prolong PFS compared to gefitinib alone, 101 while the OS benefit was not apparent.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Combatting acquired resistance to osimertinib in EGFR-mutant lung cancer

et al. 2022

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The discovery of activating mutations in epidermal growth factor receptor (EGFR) in non-small-cell lung cancer transformed the care and prognosis of patients and heralded the era of ‘personalized medicine’ in thoracic oncology. Osimertinib, a third-generation EGFR inhibitor, has been established as the preferred EGFR inhibitor for newly diagnosed patients which urged the need to develop treatment options for patients progressing on first-line osimertinib. However, acquired resistance invariably emerges and numerous efforts have been attempted to delay or overcome acquired resistance. In this article, we thoroughly reviewed the current understanding of osimertinib resistance mechanisms and explored the established and emerging treatment options. Newer treatment strategies targeting EGFR-dependent or -independent resistance mechanisms, novel approaches using bispecific antibodies and antibody–drug conjugates will be discussed. Moreover, what to do with brain only progression, and how to incorporate immunotherapy in EGFR-mutant lung cancer will be discussed. Lastly, future perspectives on the ongoing clinical trials and combination of front-line therapy will be introduced.

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“…12,13 Two randomized phase 2 trials, WJOG8715L and BOOSTER, both revealed that there was no PFS benefit of bevacizumab plus osimertinib over osimertinib in secondline EGFR T790M mutation population. 14,15 In this issue of the Journal of Thoracic Oncology, Kenmotsu et al 16 present the first randomized study comparing bevacizumab plus osimertinib with osimertinib in the first-line setting-WJOG9717L. The primary end point, PFS, was 22.1 months in bevacizumab plus osimertinib versus 20.2 months in osimertinib arm, and there was no statistically significant difference (HR ¼ 0.862, p ¼ 0.213).…”

mentioning

confidence: 99%

Antiangiogenesis May Not Be a Universal Booster of EGFR Tyrosine Kinase Inhibitors

Lin

2022

Journal of Thoracic Oncology

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Randomized Phase 2 Study of Osimertinib Plus Bevacizumab Versus Osimertinib for Untreated Patients With Nonsquamous NSCLC Harboring EGFR Mutations: WJOG9717L Study

Cited by 70 publications

References 28 publications

Case report: Almonertinib in combination with bevacizumab for leptomeningeal metastases from epidermal growth factor receptor-mutation non-small cell lung cancer: Case series

Case report: Almonertinib in combination with bevacizumab for leptomeningeal metastases from epidermal growth factor receptor-mutation non-small cell lung cancer: Case series

Combatting acquired resistance to osimertinib in EGFR-mutant lung cancer

Antiangiogenesis May Not Be a Universal Booster of EGFR Tyrosine Kinase Inhibitors

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