Outcome of Patients with NSCLC and Brain Metastases Treated with Immune Checkpoint Inhibitors in a ‘Real-Life’ Setting

Skribek, Marcus; Rounis, Konstantinos; Makrakis, Dimitrios; Agelaki, Sofia; Mavroudis, Dimitris; Petris, Luigi De; Ekman, Simon; Tsakonas, Georgios

doi:10.3390/cancers12123707

Cited by 17 publications

(10 citation statements)

References 32 publications

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“…Moreover, the discordance of treatment response between intracranial and extracranial lesions should also be noted. The discordance rate was 15.8% in our study, which was consistent with other previous studies ranging from 12.7% to 36.4% ( 16 , 33 , 34 ). The reason for the discordant outcome may be the difference in the tumor microenvironment between primary tumors and BMs.…”

Section: Discussionsupporting

confidence: 93%

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Efficacy of immune checkpoint inhibitor therapy in EGFR mutation-positive patients with NSCLC and brain metastases who have failed EGFR-TKI therapy

Zhou

Ren²,

Meng³

2022

Front. Immunol.

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BackgroundFew treatment options are available for brain metastases (BMs) in EGFR-mutant non-small cell lung cancer (NSCLC) that progress with prior EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy. This study aimed to evaluate the efficacy of immune checkpoint inhibitor (ICI) therapy in these patients.MethodsNSCLC patients with confirmed sensitive EGFR mutations and BMs were retrospectively reviewed. All patients experienced failure of EGFR-TKI therapy and were divided into two cohorts based on subsequent treatment. Cohort 1 included patients who received ICI therapy, while cohort 2 included patients treated with chemotherapy. Overall and intracranial objective response rates (ORRs) were used to evaluate the treatment response. Overall and intacranial progression-free survival (PFS) were calculated by Kaplan−Meier analysis and compared with the log-rank test. Univariate and multivariate Cox analyses were used to identify prognostic factors.ResultsA total of 53 patients treated with ICI therapy and 40 patients treated with chemotherapy were included in cohorts 1 and 2, respectively. In cohort 1, the overall ORR was 20.8%, with a median overall PFS of 4.2 months. The median intracranial PFS was 5.1 months. Of the 38 patients with measurable intracranial lesions, the intracranial ORR was 21.0%. Patients who received ICI combined with chemotherapy had the highest intracranial ORR of 37.5%. Compared to patients treated with chemotherapy in cohort 2, patients receiving ICI combined with chemotherapy had both longer intracranial PFS (6.4 vs. 5.1 months, p = 0.110) and overall PFS (6.2 vs. 4.6 months, p = 0.054), and these differences approached statistical significance. Univariate and multivariate Cox analyses demonstrated that high disease burden (p = 0.019), prior third-generation EGFR-TKI therapy (p = 0.019), and a poor lung immune prognostic index (LIPI) (p = 0.012) were independent negative predicators of overall PFS and that multiple BMs were negatively correlated with intracranial PFS among patients treated with ICI therapy.ConclusionsOur results suggested that ICI combined with chemotherapy had potent intracranial efficacy and may be a promising treatment candidate in EGFR-mutant NSCLC patients with BMs for whom prior EGFR-TKI therapy failed.

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Section: Discussionsupporting

confidence: 93%

“…Another tumor characteristic affecting patient outcomes is disease burden. We found that a high disease burden, defined as three or more metastatic organs, was an independent negative predictor for both intracranial and extracranial PFS, which is consistent with previous studies ( 33 ).…”

Section: Discussionsupporting

confidence: 92%

Efficacy of immune checkpoint inhibitor therapy in EGFR mutation-positive patients with NSCLC and brain metastases who have failed EGFR-TKI therapy

Zhou

Ren²,

Meng³

2022

Front. Immunol.

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“…Another important nding of our study was that only 32% of patients showed concordant outcomes between intracranial and extracranial responses. The discordant rate was 20%, which was similar to those reported in previous studies (22% (Goldberg et al 2020) and 24% (Skribek et al 2020)). One possible explanation of the discordance is the genetic distinction between the primary disease and brain metastatic lesions.…”

Section: Discussionsupporting

confidence: 90%

Central nervous systemic efficacy of immune checkpoint inhibitors and concordance between intra/extracranial response in non-small cell lung cancer patients with brain metastasis

Kang

Jeong

Park

et al. 2022

J Cancer Res Clin Oncol

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Purposes: Immune checkpoint inhibitors (ICIs) markedly improve the clinical outcomes of advanced nonsmall-cell lung cancer (NSCLC). However, the intracranial e cacy of ICI is not well elucidated, and previous studies showed discordant outcomes of ICI between intracranial and extracranial diseases. We aimed to evaluate the clinical outcomes and the intracranial and extracranial response of patients with NSCLC and brain metastasis who were treated with ICI in the real-world setting.Methods: A total of 55 patients (median age, 63 years [range, 42-80]; male, 78%) who had NSCLC with brain metastasis and treated with ICI monotherapy were retrospectively analyzed. We separately assessed the response rates of brain lesions and systemic lesions, and estimated the overall survival (OS) and progression-free survival (PFS).Results: The median OS and overall PFS were 17.0 months (95% CI, 10.3-25.6) and 3.19 months (95% CI, 2.24-5.03), respectively. The intracranial objective response rate and disease control rate of ICI were 36% and 54%, respectively. Among the 44 patients who showed disease progression, only 32% (n = 14) showed concordant outcomes and 9 patients (20%) showed opposing discordant outcomes. Eight patients continued ICI with local brain therapy after intracranial progression, and their median extracranial PFS and OS were 15 months (95% CI, 5.0-not assessed [NA]) and 23.8 months (95% CI, 14.7-NA), respectively.Conclusions: ICI monotherapy had a clinically meaningful intracranial e cacy in NSCLC patients with brain metastasis. Watchful waiting and close monitoring without local radiotherapy might be feasible in NSCLC patients with asymptomatic active brain metastasis.

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“…The role of ICIs in BM has been studied in retrospective analysis, case series, and preliminary clinical trials. These discoveries and their quick translation into clinical practice are causing significant shifts in treating patients with BM from NSCLC ( 85 ). Multiple studies have consistently shown that ICIs improve overall survival in both primary tumors and BM, supporting the utility of ICIs in the treatment of BM ( 88 ).…”

Section: Recent Advancements In the Treatment Of Bm From Nsclc With I...mentioning

confidence: 99%

Tumor Immune Microenvironment and Immunotherapy in Brain Metastasis From Non-Small Cell Lung Cancer

Wang

Chen

et al. 2022

Front. Immunol.

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Brain metastasis (BM), a devastating complication of advanced malignancy, has a high incidence in non-small cell lung cancer (NSCLC). As novel systemic treatment drugs and improved, more sensitive imaging investigations are performed, more patients will be diagnosed with BM. However, the main treatment methods face a high risk of complications at present. Therefore, based on immunotherapy of tumor immune microenvironment has been proposed. The development of NSCLC and its BM is closely related to the tumor microenvironment, the surrounding microenvironment where tumor cells live. In the event of BM, the metastatic tumor microenvironment in BM is composed of extracellular matrix, tissue-resident cells that change with tumor colonization and blood-derived immune cells. Immune-related cells and chemicals in the NSCLC brain metastasis microenvironment are targeted by BM immunotherapy, with immune checkpoint inhibition therapy being the most important. Blocking cancer immunosuppression by targeting immune checkpoints provides a suitable strategy for immunotherapy in patients with advanced cancers. In the past few years, several therapeutic advances in immunotherapy have changed the outlook for the treatment of BM from NSCLC. According to emerging evidence, immunotherapy plays an essential role in treating BM, with a more significant safety profile than others. This article discusses recent advances in the biology of BM from NSCLC, reviews novel mechanisms in diverse tumor metastatic stages, and emphasizes the role of the tumor immune microenvironment in metastasis. In addition, clinical advances in immunotherapy for this disease are mentioned.

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Outcome of Patients with NSCLC and Brain Metastases Treated with Immune Checkpoint Inhibitors in a ‘Real-Life’ Setting

Cited by 17 publications

References 32 publications

Efficacy of immune checkpoint inhibitor therapy in EGFR mutation-positive patients with NSCLC and brain metastases who have failed EGFR-TKI therapy

Efficacy of immune checkpoint inhibitor therapy in EGFR mutation-positive patients with NSCLC and brain metastases who have failed EGFR-TKI therapy

Central nervous systemic efficacy of immune checkpoint inhibitors and concordance between intra/extracranial response in non-small cell lung cancer patients with brain metastasis

Tumor Immune Microenvironment and Immunotherapy in Brain Metastasis From Non-Small Cell Lung Cancer

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