Efficacy of Osimertinib in EGFR-Mutated Non-Small Cell Lung Cancer with Leptomeningeal Metastases Pretreated with EGFR-Tyrosine Kinase Inhibitors

Saboundji, K.; Auliac, J.B.; Pérol, Maurice; François, G; Janicot, Henri; Marcq, M.; Dubos-Arvis, Catherine; Renault, Aldo; Guisier, Florian; Odier, L.; Gervais, Radj; Chouaïd, C.

doi:10.1007/s11523-018-0581-2

Cited by 42 publications

(36 citation statements)

References 23 publications

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“…Moreover, of 62 patients treated with EGFR‐TKIs, 11 (17.7%) received third‐generation EGFR‐TKIs, and the survival outcomes in these patients were significantly longer than with other treatments, including first‐generation EGFR‐TKIs and cytotoxic chemotherapy. These findings support the efficacy of third‐generation EGFR‐TKIs in patients with LMC, which is in line with previously published data . Approval of third‐generation EGFR‐TKIs as a first‐line chemotherapeutic regimen in EGFR‐mutant adenocarcinoma will confer a further survival benefit in patients with LMC from NSCLC.…”

Section: Discussionsupporting

confidence: 90%

Impact of clinicopathologic features on leptomeningeal metastasis from lung adenocarcinoma and treatment efficacy with epidermal growth factor receptor tyrosine kinase inhibitor

et al. 2020

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Background: We investigated the risk factors for leptomeningeal carcinomatosis (LMC) and compared clinical efficacies of various treatment modalities including intrathecal (IT) chemotherapy in patients with lung adenocarcinoma harboring epidermal growth factor receptor (EGFR) mutations. Methods: Using clinical research data from the Asan Medical Center, we retrospectively analyzed data of patients diagnosed with LMC, confirmed via cerebrospinal fluid (CSF) analysis from January 2008 to December 2017. Results: We identified 1189 patients with lung adenocarcinoma harboring EGFR mutations. Among these, 9.8% had a median duration of 13.5 (interquartile range [IQR] 6.8-23.6) months from the initial lung cancer diagnosis to LMC occurrence. Younger age (hazard ratio [HR] 1.043, P < 0.001), initial metastatic disease (HR 3.768, P < 0.001), and metastasis to the brain (HR 8.682, P < 0.001) or lung (HR 2.317, P = 0.004) were risk factors associated with LMC. Median survival duration from LMC diagnosis was 3.8 (IQR 1.5-8.6) months. Eastern Cooperative Oncology Group performance status score ≤ 2 (HR 0.505, P = 0.007) and insertion of Ommaya reservoir (HR 0.445, P = 0.005) were associated with longer survival. EGFR-tyrosine kinase inhibitor (TKI) conferred survival benefits compared to cytotoxic chemotherapy or best supportive care (HR 2.222, P = 0.018; HR 5.638, P < 0.001, respectively). Although IT chemotherapy showed no survival benefit, it was associated with improved neurologic symptoms and signs and CSF negative conversion. Conclusions: Younger age, initial diagnosis of metastatic disease, and metastasis to the brain or different lobes were associated with LMC in patients with EGFRmutant lung adenocarcinoma. Therapeutic interventions including EGFR-TKIs, cytotoxic chemotherapy, or Ommaya reservoir, and good performance status were related to favorable survival outcomes. Key pointsAge and disease status were associated with LMC in patients with EGFR-mutant adenocarcinoma, and EGFR-TKI, Ommaya reservoir, and good performance status were related to survival benefit. 436

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Section: Discussionsupporting

confidence: 90%

Impact of clinicopathologic features on leptomeningeal metastasis from lung adenocarcinoma and treatment efficacy with epidermal growth factor receptor tyrosine kinase inhibitor

et al. 2020

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“…30 In a retrospective study of 20 patients with EGFRm NSCLC and LM (initial osimertinib dose: 80 mg, n ¼ 17; 160 mg, n ¼ 2; 40 mg, n ¼ 1), the median PFS and OS were 17.3 and 18.0 months, respectively. 31 Additional prospective studies are needed to confirm these findings. The clinical efficacy of osimertinib is superior to that reported for firstand second-generation EGFR-TKIs in patients with EGFRm NSCLC and LM.…”

Section: Discussionmentioning

confidence: 96%

Osimertinib for Patients With Leptomeningeal Metastases Associated With EGFR T790M-Positive Advanced NSCLC: The AURA Leptomeningeal Metastases Analysis

Ahn

Chiu

Cheng

et al. 2020

Journal of Thoracic Oncology

106

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Introduction: Osimertinib has shown promising activity in patients with leptomeningeal metastases (LMs) of EGFRpositive NSCLC at 160 mg once daily (qd) (BLOOM; NCT02228369). We report LM activity with osimertinib (80 mg qd) in a retrospective analysis of studies across the AURA program (AURA extension, AURA2, AURA17, and AURA3). Methods: Patients with EGFR T790M-positive advanced NSCLC and progression after previous EGFR-tyrosine kinase inhibitor therapy received osimertinib (80 mg qd). Patients with central nervous system (CNS) metastases (including LMs) were eligible if the lesions were neurologically asymptomatic and stable. Patients with evidence of LMs at the study entry were retrospectively included for the analysis; brain scans were assessed for radiologic LM response by neuroradiologically blinded, independent central review per the modified Response Assessment in Neuro-Oncology LM criteria. LM objective response rate, duration of response, progression-free survival, and overall survival were assessed. A longitudinal analysis was performed to investigate the relationship between changes from the baseline in non-CNS tumor sizes and LM responses at each visit of patients in AURA LM and BLOOM studies. Results: For the 22 patients included in the analysis, LM objective response rate was 55% (95% confidence interval [CI]: 32-76). Median LM duration of response was not reached (95% CI: 2.8-not calculable [NC]). Median LM progression-free survival and overall survival were 11.1 months (95% CI: 4.6-NC) and 18.8 months (95% CI: 6.3-NC), respectively. The longitudinal analysis revealed similar non-CNS and LM responses between the patients in AURA LM and BLOOM programs. Conclusions: Patients with EGFR T790M-positive NSCLC and radiologically detected LM obtained clinical benefit from osimertinib (80 mg qd).

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“…The intracranial objective response rate (ORR) was 62% (95%CI: 45-78), the median OS was 11.0 months (95%CI: 8.0-18.0 months), and a CSF tumor cell clearance was confirmed in 11 patients (28%) [104] . Saboundji et al [105] retrospectively analyzed a cohort of 20 patients treated with osimertinib: all patients (100%) displayed neurological improvement, and 5 patients (20%) showed prompt radiological response within 15 days from the start of treatment. For this cohort, median PFS and OS were of 17.2 and 18 months, respectively.…”

Section: Role Of Egfr Tyrosine Kinase Inhibitors In Lm From Nsclcmentioning

confidence: 99%

“…Osimertinib 160 mg daily 20/23 patients (86.9%) had neurological improvement 23/32 (72%) had radiological response Nanjo et al [17] , 2017 Yang et al [104] , 2020 Saboundji et al [105] , 2018 Ahn et al [106] , 2020…”

mentioning

confidence: 99%

Leptomeningeal metastases from non-small cell lung cancer: state of the art and recent advances

Pellerino¹,

Internò²,

Muscolino³

et al. 2020

JCMT

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Patients with leptomeningeal metastases (LM) from non-small cell lung cancer (NSCLC) have a poor outcome with survival of less than 1 year regardless of advancements in treatment strategy. In the past, some randomized clinical trials have been conducted with heterogeneous inclusion criteria, diagnostic parameters, response evaluation and primary endpoints. Efforts to develop a standardized magnetic resonance imaging (MRI) assessment and liquid biopsy techniques to monitor disease evolution in plasma or cerebrospinal fluid (CSF) are underway. This review aims to cover the main clinical and diagnostic challenges of LM from NSCLC, in particular the role of MRI, CSF cytology and liquid biopsy for the diagnosis and monitoring of the disease, as well as the most recent clinical trials on targeted therapies. Targeted therapy, such as epidermal growth factor receptor tyrosine kinase inhibitors and anaplastic lymphoma kinase rearranged inhibitors, represent a feasible treatment with encouraging results in terms of disease control and survival. For ineligible patients, immune checkpoint inhibitors could represent a therapeutic option with acceptable tolerance, although clinical trials focused on LM from NSCLC are lacking and represent a research focus for the future.

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Efficacy of Osimertinib in EGFR-Mutated Non-Small Cell Lung Cancer with Leptomeningeal Metastases Pretreated with EGFR-Tyrosine Kinase Inhibitors

Abstract: In this non-selected population, osimertinib had remarkable efficacy in NSCLC patients with LM irrespective of the presence of the EGFR-T790M-resistance mutation. Osimertinib efficacy was rapid in several patients, even some with poor performance status.

Cited by 42 publications

References 23 publications

Impact of clinicopathologic features on leptomeningeal metastasis from lung adenocarcinoma and treatment efficacy with epidermal growth factor receptor tyrosine kinase inhibitor

Impact of clinicopathologic features on leptomeningeal metastasis from lung adenocarcinoma and treatment efficacy with epidermal growth factor receptor tyrosine kinase inhibitor

Osimertinib for Patients With Leptomeningeal Metastases Associated With EGFR T790M-Positive Advanced NSCLC: The AURA Leptomeningeal Metastases Analysis

Leptomeningeal metastases from non-small cell lung cancer: state of the art and recent advances

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