&lt;p&gt;PD-1/PD-L1 Inhibitor Combined with Chemotherapy Can Improve the Survival of Non-Small Cell Lung Cancer Patients with Brain Metastases&lt;/p&gt;

Sun, Chengtao; Zhou, Fei; Li, Xuefei; Zhao, Chao; Li, Wei; Li, Jiayu; Xiong, Anwen; Yu, Jia; Gao, Guanghui; Wang, Qi; Wu, Fengying; Zhou, Caicun

doi:10.2147/ott.s286600

“…The difference in the results might because of the inclusion of more studies and varying sample sizes. In a retrospective study [ 44 ], 77 patients with NSCLC with BM who received either immune combination chemotherapy or monotherapy were included. The results of subgroup analysis revealed that chemotherapy combined with ICIs led to a significantly superior OS rate compared with ICIs alone.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of PD-1/PD-L1 Inhibitors versus Chemotherapy in Lung Cancer with Brain Metastases: A Systematic Review and Meta-Analysis

Yang

¹

,

Zeng

²

,

Tan

³

et al. 2022

Journal of Immunology Research

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Immune checkpoint inhibitors (ICIs) are widely used to treat local or metastatic lung cancer. However, the efficacy of ICI in patients with brain metastases (BM) from lung cancer is unknown. This study aimed to evaluate the efficacy of PD-1/PD-L1 ICIs compared with chemotherapy for patients with lung cancer with BM. Electronic databases (PubMed, Embase, The Cochrane Library, and Web of Science) were searched. The meta-analysis assessed overall survival (OS) and progression-free survival (PFS) of the PD-1/PD-L1 inhibitors axis and its relationship with pathological type, drug modality, and the treatment line number in patients with BM from lung cancer. We included 694 patients with BM from lung cancer from 11 randomized controlled trials. Statistical analysis showed that compared with chemotherapy, PD-1/PD-L1 inhibitors could significantly prolong OS ( hazard ratio HR = 0.75 , 95 % confidence interval 95 % CI = 0.51 – 0.99 ) and PFS ( HR = 0.65 , 95 % CI = 0.51 – 0.80 ). In the subgroup analysis, ICIs plus chemotherapy improved PFS ( HR = 0.60 , 95 % CI = 0.40 – 0.80 ), but not OS ( HR = 0.75 , 95 % CI = 0.30 – 1.19 ). The efficacy of ICI monotherapy in patients with BM was significantly different between OS and PFS: OS pooled HR = 0.81 ( 95 % CI = 0.57 – 1.05 ) and PFS = 0.78 ( 95 % CI = 0.62 – 0.94 ). Among different pathological types, the OS pooled HR was 0.67 (9 5 % CI = 0.39 – 0.95 ) for non-small cell lung cancer (NSCLC) and 0.94 ( 95 % CI = 0.56 – 1.33 ) for small cell lung cancer (SCLC); the PFS pooled HR was 0.58 ( 95 % CI = 0.39 – 0.76 ) for NSCLC and 0.79 ( 95 % CI = 0.65 – 0.93 ) for SCLC. Subgroups analysis of treatment line showed that no advantage for OS with ICIs as first-line or subsequent-line therapy, whereas ICIs as first-line ( HR = 0.63 , 95 % CI = 0.53 – 0.74 ) and second-line ( HR = 0.62 , 95 % CI = 0.62 – 0.96 ) benefitted PFS. This meta-analysis implied that compared with chemotherapy, PD-1/PD-L1 inhibitors significantly improved efficacy treatment of patients with BM from lung cancer. Further studies are needed to confirm the role of ICIs in different pathological types and drug treatment modalities.

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“…However, most active or untreated BM patients have been excluded from clinical trials. The intracranial response has not been determined in less‐selected patients with BM 20,47,48 . Additionally, a meta‐analysis by Yang et al 49 found that patients with BM who underwent ICIs combined with chemotherapy only experienced superior OS, but not PFS or iPFS than chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…The intracranial response has not been determined in less‐selected patients with BM. 20 , 47 , 48 Additionally, a meta‐analysis by Yang et al 49 found that patients with BM who underwent ICIs combined with chemotherapy only experienced superior OS, but not PFS or iPFS than chemotherapy. Sun et al 47 suggested that ICIs combined with chemotherapy significantly showed superior survival (iPFS, PFS, and OS) than ICI monotherapy.…”

Section: Discussionmentioning

confidence: 99%

“… 20 , 47 , 48 Additionally, a meta‐analysis by Yang et al 49 found that patients with BM who underwent ICIs combined with chemotherapy only experienced superior OS, but not PFS or iPFS than chemotherapy. Sun et al 47 suggested that ICIs combined with chemotherapy significantly showed superior survival (iPFS, PFS, and OS) than ICI monotherapy. This study found that ICIs combined with chemotherapy group prolonged OS compared with ICI monotherapy group, and baseline characteristics of patients between these two groups were equally.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Efficacy of PD‐1/PD‐L1 inhibitors in patients with non‐small cell lung cancer and brain metastases: A real‐world retrospective study in China

Sheng

¹

,

Li

²

,

Yu

³

et al. 2021

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Background There is only limited knowledge of the treatment responses and clinical outcomes of immune checkpoint inhibitors (ICIs) in driver gene‐negative non‐small cell lung cancer (NSCLC) patients with brain metastases (BM). This study aims to assess the efficacy of immunotherapy in these patients in a real world setting. Methods NSCLC‐BM patients without driver gene mutations who received ICIs were retrospectively identified between July 2017 and December 2019. The primary observation endpoint was intracranial objective response rate (iORR), and secondary objectives were objective response rate (ORR), intracranial and systemic progression‐free survival (iPFS, PFS), and overall survival (OS). Results We reviewed 1578 patients with lung cancer and BM. According to the exclusion criteria, 41 patients were finally enrolled. Among these 41 patients, iORR was 36.6% (95% confidence interval [CI] = 21.2%–52.0%), whereas iPFS was 6.8 (95% CI = 3.32–10.35) months. Additionally, ORR, PFS, and OS were 24.4% (95% CI = 10.7%–38.1%), 6.2 (95% CI = 4.57–7.83) months and 13.7 (95% CI = 11.20–16.26) months, respectively. ICIs combined with concurrent radiotherapy group exhibited preferred iORR (p = 0.030) compared with no radiotherapy group, and ICIs plus chemotherapy showed improved OS (p = 0.024) compared to ICI monotherapy. Moreover, the lines of ICI treatment ≥2 (p = 0.005) and derived neutrophil‐to‐lymphocyte ratio (dNLR) ≥3 (p = 0.010) were independently negative factors for OS. Conclusion In NSCLC‐BMs patients lacking driver genes, ICIs exhibited an effective drug regime. A combination of ICIs with concurrent radiotherapy showed a better intracranial response, whereas ICIs plus chemotherapy were associated with superior OS.

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“…As a result, immunotherapy for BM from NSCLC is being developed with other combination therapies, such as radiotherapy or chemotherapy (92)(93)(94)(95). Recent research has discovered that cancer patients having radiotherapy and/or chemotherapy have varied immunogenicity patterns, which could improve the function of immunotherapy, promote efficiency, and reduce side effects (96)(97)(98). Because of their potential to influence innate and adaptive immunity, certain chemotherapeutic drugs, such as cyclophosphamide, may improve the anticancer efficacy of immunotherapy.…”

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

¹

,

Chen

²

,

Wa

³

et al. 2022

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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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<p>PD-1/PD-L1 Inhibitor Combined with Chemotherapy Can Improve the Survival of Non-Small Cell Lung Cancer Patients with Brain Metastases</p>

Cited by 8 publications

References 41 publications

Efficacy of PD-1/PD-L1 Inhibitors versus Chemotherapy in Lung Cancer with Brain Metastases: A Systematic Review and Meta-Analysis

Efficacy of PD-1/PD-L1 Inhibitors versus Chemotherapy in Lung Cancer with Brain Metastases: A Systematic Review and Meta-Analysis

Efficacy of PD‐1/PD‐L1 inhibitors in patients with non‐small cell lung cancer and brain metastases: A real‐world retrospective study in China

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

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