Dynamics of eligibility criteria for central nervous system metastases in non-small cell lung cancer randomized clinical trials over time: A systematic review

Schoenmaekers, Janna; Dursun, Safiye; Biesmans, Charlotte; Ruysscher, Dirk K.M. De; Broen, Martijn P. G.; Remón, Jordi; Dingemans, Anne‐Marie C.; Hendriks, L.

doi:10.1016/j.critrevonc.2021.103460

Cited by 6 publications

(5 citation statements)

References 48 publications

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“…Nonetheless, limitations in most of the clinical studies performed so far constrain our understanding of ICI efficacy in NSCLC. Specific limitations include: (i) patients with BM were systematically excluded from most studies [ 84 , 120 ] or analyzed only in subgroup analyses for which they represented less than 20% of the samples [ 121 , 122 , 123 , 124 ], (ii) the analyzed BM samples are small and suffer selection biases and poorly-defined inclusion criteria [ 125 ], (iii) the intracranial efficacy of ICI has so far been assessed with retrospective studies only, (iv) no studies have addressed the efficacy of ICI in patients with symptomatic BM, and (v) there is limited data about ICI monotherapy and CNS efficacy [ 126 ]. CheckMate 227, evaluating the combination of ipilimumab and nivolumab in patients with advanced NSCLC, did enroll a large number of patients with brain metastases (81/793) and did show a trend towards benefits in this subgroup [ 127 ].…”

Section: Ici For Brain Metastasesmentioning

confidence: 99%

The Current Landscape of Immune Checkpoint Inhibitor Immunotherapy for Primary and Metastatic Brain Tumors

Alimonti

Castro

2023

Antibodies

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Antibodies against immune checkpoint inhibitors (ICIs) have revolutionized the treatment of multiple aggressive malignancies, including melanoma and non-small cell lung cancer. ICIs for the treatment of primary and metastatic brain tumors have been used with varying degrees of success. Here, we discuss the available evidence for the use of ICIs in the treatment of primary and metastatic brain tumors, highlighting challenges and opportunities for furthering this type of cancer immunotherapy in neuro-oncology.

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Section: Ici For Brain Metastasesmentioning

confidence: 99%

The Current Landscape of Immune Checkpoint Inhibitor Immunotherapy for Primary and Metastatic Brain Tumors

Alimonti

Castro

2023

Antibodies

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“…With the increasing incidence of patients with brain metastases and the emergence of clinical trials that either include or are specifically designed for patients with brain metastases, the paradigm is slowly changing. 115,116 Despite these limitations, the most recent clinical guidelines agree that patients with NSCLC and asymptomatic brain metastases should be treated with upfront personalized treatment if a targetable oncogenic driver exists or with an ICI-based strategy for patients without oncogenic drivers. 75,110,111 The available data supporting these recommendations is summarized below with further details regarding TKIs and CNS activity provided in Table 3.…”

Section: Systemic Treatment Of Nsclc Brain Metastasesmentioning

confidence: 99%

“…Most of the existing data establishing the CNS activity of TKI in oncogenic addicted NSCLC is derived from trials not designed to robustly generate such data, as baseline screening for brain metastases was not always mandated and stratification often did not occur. 115,117 With the firstgeneration EGFR inhibitors such as erlotinib, gefitinib, and icotinib, CNS relapses occurred frequently due to pharmacologic failure as blood-brain barrier penetration of these TKIs is poor. Data for second-generation EGFR-TKIs is scarce and lacking for dacomitinib but suggests a higher intracranial activity compared with first-generation EGFR-TKIs.…”

Section: Systemic Treatment Of Nsclc Brain Metastasesmentioning

confidence: 99%

“…183 However, almost all pivotal phase III trials excluded patients with untreated brain metastases, and the percentage of patients with treated brain metastases included in these trials was well below 20%. 115,184,185 In a pooled analysis of the KEYNOTE-001, -010, -024, and -42 trials, pembrolizumab compared with chemotherapy improved OS for patients with and without brain metastases. The benefit seemed more pronounced in patients with a PD-L1 expression level of 50% or more (HR, 0.67; 95% CI, 0.44-1.02), versus 1% or more (HR, 0.83; 95% CI, 0.62-1.10).…”

Section: Systemic Treatment Of Nsclc Brain Metastasesmentioning

confidence: 99%

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Emerging Systemic Treatment Perspectives on Brain Metastases: Moving Toward a Better Outlook for Patients

Alvarez‐Breckenridge

Remón

Piña

et al. 2022

American Society of Clinical Oncology Educational Book

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The diagnosis of brain metastases has historically been a dreaded, end-stage complication of systemic disease. Additionally, with the increasing effectiveness of systemic therapies that prolong life expectancy and improved imaging tools, the incidence of intracranial progression is becoming more common. Within this context, there has been increasing attention directed at understanding the molecular underpinnings of intracranial progression. Exploring the unique features of brain metastases compared with their extracranial counterparts to identify aberrant signaling pathways, which can be targeted pharmacologically, may help lead to new treatments for this patient population. Additionally, critical discoveries outside the sphere of the central nervous system are increasingly being applied to brain metastases with the emergence of immune checkpoint inhibition, becoming a prevalent treatment option for patients with brain metastases across multiple histologies. As novel treatment strategies are considered, they require thoughtful incorporation of agents that can cross the blood-brain barrier and can synergize with pre-existing agents through rational combinations. Lastly, as clinicians and scientists continue to understand key molecular features of these tumors, they will continue to influence the treatment algorithms that are developing for the management of these patients. Due to the complexity of treatment decisions for patients with brain metastases, an emerging tool is the utilization of multidisciplinary brain metastasis tumor boards to ensure optimal treatment decisions are made and that patients are provided access to applicable clinical trials. Looking to the future, the collective effort to understand the various tumor-intrinsic and tumor-extrinsic factors that promote central nervous system seeding and propagation will have the potential to change the clinical trajectory for these patients.

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“…The conventional therapies for NSCLC with BM include surgery, radiation and chemotherapy with a median overall survival (mOS) ranging from 4.0 to 31.0 months [4]. The introduction of tyrosine kinase inhibitors and the immune checkpoint inhibitors has improved the 5-year survival rate from 30-60% in selected patients with metastatic NSCLC [5]. NSCLC with de novo BM has been recognized as an entity with heterogeneous prognosis[6] and its risk strati cation is a critical component of standard management.…”

Section: Introductionmentioning

confidence: 99%

A Prognostic Nomogram via Competing Risk Model with Patterns of Extracranial Metastasis in Elderly NSCLC Patients with Synchronous Brain-metastasis: A Large Population-based Study

Zhang

Zhu

Jiang

et al. 2022

Preprint

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Introduction: To determine whether the patterns of extracranial metastasis (ECMs) provide supplementary prognositc information to DS-GPA in elderly NSCLC patients with synchronous BM. Methods: This study included 4974 NSCLC patients with initial BM diagnosed from 2010 to 2015 using the Surveillance Epidemiology and End Results (SEER) program. Patients were divided randomly into training and hold-out test sets. Patterns of ECMs were established based on the difference of survival via competing risk analysis in the training set. A nomogram prediction of 6-month, 12-month, and 18-month disease-specific survival (DSS) was built using independent prognostic factors. Results: Three patterns of ECM were recognized: MA (neither liver, bone, nor lung involvement), MB (without liver involvement), and MC (with liver involvement). Comparing MA, MB and MC showed significant correlation to survival (SHR, 1.126, 95% CI, 1.053-1.205, P<0.001; SHR, 1.46, 95% CI, 1.339-1.592, P<0.001, respectively). In the hold-out test set, the AUC of the ROC curve for the 6-month DSS prediction reached 0.778, whereas reaching 0.757 in the training set. The calibration curves did not deviate from the reference line. Decision curve analyses revealed the net benefit of the nomogram for clinical utility. Conclusions: These results help clinicians make decisions for brain-metastatic NSCLC in the era of precision therapy. The risk stratification of extracranial involvements indicates differential treatment for elderly NSCLC patients with synchronous brain-metastasis.

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Dynamics of eligibility criteria for central nervous system metastases in non-small cell lung cancer randomized clinical trials over time: A systematic review

Cited by 6 publications

References 48 publications

The Current Landscape of Immune Checkpoint Inhibitor Immunotherapy for Primary and Metastatic Brain Tumors

The Current Landscape of Immune Checkpoint Inhibitor Immunotherapy for Primary and Metastatic Brain Tumors

Emerging Systemic Treatment Perspectives on Brain Metastases: Moving Toward a Better Outlook for Patients

A Prognostic Nomogram via Competing Risk Model with Patterns of Extracranial Metastasis in Elderly NSCLC Patients with Synchronous Brain-metastasis: A Large Population-based Study

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