Opportunities and challenges of immune checkpoint inhibitors for extensive‐stage small‐cell lung cancer

Zhao, Jing; Zhuo, Xiaoli; Liu, Lei; Yang, Zhe; Fu, Guobin

doi:10.1002/cai2.23

Cited by 4 publications

(3 citation statements)

References 43 publications

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“…Immunotherapy modalities also play an important role in the survival benefit of patients. Basic studies have shown that chemotherapy is able to induce immunogenic cell death and promote tumor antigen release 22 , 23 . Bevacizumab promotes DC maturation and promotes more efficient T cell priming and activation, while it induces normalization of tumor vasculature, thereby promoting effector lymphocyte infiltration into tumor tissue 24 .…”

Section: Discussionmentioning

confidence: 99%

The Real-world Therapeutic Analysis of First-line Immunotherapy in Chinese Patients with Drive Gene Positive for Advanced Non-Small Cell Lung Cancer

Liu¹,

Li²,

Zhao³

et al. 2023

J. Cancer

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Background: Immune checkpoint inhibitors (ICIs) are widely used for treating advanced non-small cell lung cancer (NSCLC). However, some studies indicate that patients with genetic mutations do not benefit from immunotherapy. Hence, this study explored the efficacy of anti-programmed death-1 (PD-1) and anti-programmed death-ligand 1 (PD-L1) antibodies in the first-line treatment of advanced NSCLC with driver gene mutations in real-world settings. Methods: We retrospective analyzed patients with advanced NSCLC who treated with first-line anti-PD-1/PD-L1 antibodies at Shandong Provincial Hospital between May 2019 and October 2020. The patient's driver gene mutation status was identified using amplification refractory mutation system PCR (ARMS-PCR). The basic clinical characteristics, objective response rate (ORR), progression free survival (PFS), and other clinical data of patients were collected to evaluate the clinical efficacy and potential prognostic factors of treatment for patients with driver gene mutations. Results: A total of 430 patients' information was counted during this period, finally, 89 patients with NSCLC were enrolled in the study. The main pathological subtype of patients was adenocarcinoma (62.9%). The overall mutation rate was 44.9% (n = 40) and included following mutations: KRAS (n = 20), TP53 (n = 18), EGFR (n = 6), BRAF (n = 3), Her-2 (n = 3), MET (n = 3), ROS1 (n = 1), and NRAS (n = 1). The overall ORR was 44.30% and the disease control rate (DCR) was 82.23%. At the time of follow-up cut-off, the median PFS of all patients was 8.2 month. In NSCLC patients treated with ICI, median PFS was longer in mutation-negative patients than in mutation-positive patients (8.98 vs 7.07 months, P < 0.05). Survival benefit varied across mutational subgroups: KRAS patients could benefit from first-line immunotherapy (10.1 months, P < 0.05), patients with EGFR mutations have poor first-line immunotherapy outcomes, with a median PFS of only 3.0 months (P < 0.01), and patients with other mutation types having no significant difference in response from mutation-negative patients. In most mutation subgroups, immune combination therapy had longer PFS than immune monotherapy, and PD-L1 expression levels were positively correlated with clinical benefit in patients. Conclusion:In the real world, patients with KRAS mutations benefit from first-line immunotherapy, immune-combination modalities are more effective, and immune efficacy is positively correlated with PD-L1 expression; Patients with other driver mutations (BRAF, NRAS, Her2, MET, ROS1) benefit similarly to mutation-negative patients in first-line immunotherapy, and immunotherapy is recommended for first-line therapy; Immunotherapy is worse effective in patients with EGFR mutations, immunotherapy is not recommended in first-line therapy even patients with high PD-L1 expression.

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Section: Discussionmentioning

confidence: 99%

The Real-world Therapeutic Analysis of First-line Immunotherapy in Chinese Patients with Drive Gene Positive for Advanced Non-Small Cell Lung Cancer

Liu¹,

Li²,

Zhao³

et al. 2023

J. Cancer

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“…A recent meta-analysis of mostly retrospective studies, all <IIB NSCLC, showed a 1-year overall survival (OS) of 83 to 98% and 5-year OS between 22.5 and 55.7%. 43 The choice of RFA versus SABR in early-stage NSCLC remains controversial. A retrospective study of 6,195 stage 1a nonsurgical NSCLC patients found no significant difference between RFA and SABR; however, a meta-analysis including 105 studies demonstrated similar short-term survivals but better long-term survivals for SABR.…”

Section: Lung Ablationmentioning

confidence: 99%

An Interventional Radiologist's Guide to Lung Cancer

Fish,

Madoff

2024

Semin intervent Radiol

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Lung cancer continues to be the third leading cause of cancer and the leading cause of cancer deaths. As the field of interventional oncology continues to grow, interventional radiologists are increasingly treating lung cancer patients. Involvement begins with tissue diagnosis for which biomarkers and immunohistochemistry are used to guide selective and advanced medical therapies. An interventional radiologist must be aware of the rationale behind tissue diagnosis and techniques to minimize biopsy complications. Staging is an important part of tumor board conversations and drives treatment pathways. Surgical therapy remains the gold standard for early-stage disease but with an aging population the need for less invasive treatments such as radiation therapy and ablation continue to grow. The interventionalist must be aware of the indications, techniques, and pre- and posttherapy managements for percutaneous ablation. Endovascular therapy is broadly divided into therapeutic treatment of lung cancer, which is gaining traction, and treatment of lung cancer complications such as hemoptysis. This review aims to provide a good basis for interventional radiologists treating lung cancer patients.

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“…Among these therapies, immunotherapy has become the mainstream of modern cancer treatment ( 45 ) by manipulating the self-immune system to recognize and attack cancer cells and has achieved unprecedented success in clinical trials. Especially for lung cancer, as the most common cancer worldwide, the prognosis of advanced NSCLC ( 46 ) and extensive‐stage small‐cell lung cancer (SCLC) ( 47 ) was significantly improved with the administration of immunotherapy. Up to now, two PD1 inhibitors Nivolumab and Pembrolizumab and one PD-L1 inhibitor Atezolizumab have been approved as standard treatment options for NSCLC patients ( 48 ).…”

Section: Introductionmentioning

confidence: 99%

Roles and therapeutic implications of m6A modification in cancer immunotherapy

et al. 2023

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Recent studies have demonstrated that N6-methyladenosine (m6A), the most abundant, dynamic, and reversible epigenetic RNA modification in eukaryotes, is regulated by a series of enzymes, including methyltransferases (writers), demethylases (erasers), and m6A recognition proteins (readers). Aberrant regulation of m6A modification is pivotal for tumorigenesis, progression, invasion, metastasis, and apoptosis of malignant tumors. Immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, as recognized by the 2018 Nobel Prize in Medicine and Physiology. However, not all cancer patients response to ICI therapy, which is thought to be the result of intricate immune escape mechanisms. Recently, numerous studies have suggested a novel role for m6A epigenetic modification in the regulation of tumor immune evasion. Herein, we review the relevant mechanisms of m6A regulators in regulating various key signaling pathways in cancer biology and how m6A epigenetic modifications regulate the expression of immune checkpoints, opening a new window to understand the roles and mechanisms of m6A epigenetic modifications in regulating tumor immune evasion. In addition, we highlight the prospects and development directions of future combined immunotherapy strategies based on m6A modification targeting, providing directions for promoting the treatment outcomes of immune checkpoint inhibitors.

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Opportunities and challenges of immune checkpoint inhibitors for extensive‐stage small‐cell lung cancer

Cited by 4 publications

References 43 publications

The Real-world Therapeutic Analysis of First-line Immunotherapy in Chinese Patients with Drive Gene Positive for Advanced Non-Small Cell Lung Cancer

The Real-world Therapeutic Analysis of First-line Immunotherapy in Chinese Patients with Drive Gene Positive for Advanced Non-Small Cell Lung Cancer

An Interventional Radiologist's Guide to Lung Cancer

Roles and therapeutic implications of m6A modification in cancer immunotherapy

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