Comparison of a combination of chemotherapy and immune checkpoint inhibitors and immune checkpoint inhibitors alone for the treatment of advanced and metastatic non‐small cell lung cancer

Kuo, Chih-Hsi S.; Wang, Chin‐Chou; Huang, Yu‐Chen; Pavlidis, Stelios; Liu, Chien-Ying; Ko, How-Wen; Chung, Fu‐Tsai; Lin, Tzu-Chao; Wang, Chih‐Liang; Guo, Yike; Yang, Cheng‐Ta

doi:10.1111/1759-7714.13057

Cited by 18 publications

(16 citation statements)

References 33 publications

(67 reference statements)

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“…checkpoint inhibitors improves the treatment efficacy over immune checkpoint inhibitors alone 52 , indicating that combinational approaches would be the future standard treatment in NSCLC 53 . Our results suggested that administration of CCL7 through the intranasal pathway promoted the recruitment of cDC1 into the tumor-burdened lungs and subsequent expansion of CD8 + and CD4 + T cells in the bronchial LNs and tumor-burdened lungs.…”

Section: Discussionmentioning

confidence: 99%

“…Recent progresses of several phase III trials have shown that combination of anti-PD-1/PD-L1 immune checkpoint blockades plus chemo-reagents is superior to chemotherapy alone as first-line treatment for advanced NSCLC patients in regard of the OS and PFS 51 . A retrospective study shows that combination of chemotherapy and immune checkpoint inhibitors improves the treatment efficacy over immune checkpoint inhibitors alone 52 , indicating that combinational approaches would be the future standard treatment in NSCLC 53 . Our results suggested that administration of CCL7 through the intranasal pathway promoted the recruitment of cDC1 into the tumor-burdened lungs and subsequent expansion of CD8 + and CD4 + T cells in the bronchial LNs and tumor-burdened lungs.…”

Section: Discussionmentioning

confidence: 99%

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CCL7 recruits cDC1 to promote antitumor immunity and facilitate checkpoint immunotherapy to non-small cell lung cancer

et al. 2020

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The efficacy of checkpoint immunotherapy to non-small cell lung cancer (NSCLC) largely depends on the tumor microenvironment (TME). Here, we demonstrate that CCL7 facilitates anti-PD-1 therapy for the KrasLSL−G12D/+Tp53fl/fl (KP) and the KrasLSL−G12D/+Lkb1fl/fl (KL) NSCLC mouse models by recruiting conventional DC 1 (cDC1) into the TME to promote T cell expansion. CCL7 exhibits high expression in NSCLC tumor tissues and is positively correlated with the infiltration of cDC1 in the TME and the overall survival of NSCLC patients. CCL7 deficiency impairs the infiltration of cDC1 in the TME and the subsequent expansion of CD8+ and CD4+ T cells in bronchial draining lymph nodes and TME, thereby promoting tumor development in the KP mouse model. Administration of CCL7 into lungs alone or in combination with anti-PD-1 significantly inhibits tumor development and prolongs the survival of KP and KL mice. These findings suggest that CCL7 potentially serves as a biomarker and adjuvant for checkpoint immunotherapy of NSCLC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

CCL7 recruits cDC1 to promote antitumor immunity and facilitate checkpoint immunotherapy to non-small cell lung cancer

et al. 2020

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“…Anti-PD-1/PD-L1 ICIs in combination with chemotherapy may be more effective than anti-PD-1/PD-L1 ICIs alone for the treatment of advanced NSCLC [132]. Therefore, this combination therapy may be suggested as sequential treatment for patients with EGFR-mutant NSCLC who do not have known targetable acquired resistant mutations, but efficacy studies are needed.…”

Section: Future Perspectivesmentioning

confidence: 99%

Epidermal Growth Factor Receptor (EGFR) Pathway, Yes-Associated Protein (YAP) and the Regulation of Programmed Death-Ligand 1 (PD-L1) in Non-Small Cell Lung Cancer (NSCLC)

Hsu

Jablons

Yang

et al. 2019

IJMS

137

100

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The epidermal growth factor receptor (EGFR) pathway is a well-studied oncogenic pathway in human non-small cell lung cancer (NSCLC). A subset of advanced NSCLC patients (15–55%) have EGFR-driven mutations and benefit from treatment with EGFR-tyrosine kinase inhibitors (TKIs). Immune checkpoint inhibitors (ICIs) targeting the PD-1/PDL-1 axis are a new anti-cancer therapy for metastatic NSCLC. The anti-PD-1/PDL-1 ICIs showed promising efficacy (~30% response rate) and improved the survival of patients with metastatic NSCLC, but the role of anti-PD-1/PDL-1 ICIs for EGFR mutant NSCLC is not clear. YAP (yes-associated protein) is the main mediator of the Hippo pathway and has been identified as promoting cancer progression, drug resistance, and metastasis in NSCLC. Here, we review recent studies that examined the correlation between the EGFR, YAP pathways, and PD-L1 and demonstrate the mechanism by which EGFR and YAP regulate PD-L1 expression in human NSCLC. About 50% of EGFR mutant NSCLC patients acquire resistance to EGFR-TKIs without known targetable secondary mutations. Targeting YAP therapy is suggested as a potential treatment for NSCLC with acquired resistance to EGFR-TKIs. Future work should focus on the efficacy of YAP inhibitors in combination with immune checkpoint PD-L1/PD-1 blockade in EGFR mutant NSCLC without targetable resistant mutations.

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“…However, recent studies have found that chemotherapy may have immunomodulatory properties, which can be induced by the tumor microenvironment from the immune desert or immune excluded to a state conducive to the role of immune cells ( 33 ). Even if the proportion of patients with EGFR or ALK mutations increases, chemotherapy may provide some survival benefits ( 34 ).…”

Section: Discussionmentioning

confidence: 99%

The Effectiveness and Safety of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer Patients With Stage III/IV: A Multicenter Study

et al. 2021

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Immune checkpoint inhibitors (ICIs) have been approved to treat patients with various cancer types, including lung cancer, in many countries. This study aims to investigate the effectiveness and safety of ICIs under different treatment conditions of non-small cell lung cancer patients. A population-based retrospective cohort study was conducted using the electronic health records of three medical centers in Taiwan. From January 01, 2016, to November 30, 2018, a total of 91 ICIs and 300 traditional chemotherapy users who had undergone stage III and IV lung cancer treatment were included in the study. We performed the randomized matched pair design by selecting a Chemotherapy subject for each ICI patient in the sample population. All subjects were monitored from the date of taking ICIs or chemotherapy drugs until the event of death, loss to follow-up, or were occurred with any defined adverse events. Kaplan-Meier estimators and cox proportional hazard regression models were used to compute the overall survival, efficacy, and safety of the ICIs group. The median overall survival (OS) in the ICI and Chemo groups after matching was 11.2 months and 10.5 months, respectively. However, the results showed no significant OS differences between ICIs and chemo groups for both before and after matching (HR,1.30; 95%CI, 0.68-2.46; p=0.428 before matching and HR,0.96; 95CI%, 0.64-1.44; p=0.838 after matching). We observed that with the higher amount of PD-L1, the length of the patients’ overall survival was (positive vs. negative PD-L1, HR,0.21; 95%CI, 0.05-0.80; p=0.022). The incidences of serious adverse drug events above grade 3 in the ICIs and traditional chemo groups were 12.7% and 21.5%, respectively. We also found that the number of AEs was less in ICIs than in the Chemo group, and the AEs that occurred after treatments were observed earlier in the ICIs compared to the Chemo group. ICIs drugs were observed to be safer than traditional chemotherapy as they had a lower risk of serious adverse drug events. It is necessary to pay attention to immune-related side effects and provide appropriate treatment. Furthermore, the patient’s physical status and PD-L1 test can be used to evaluate the clinical effectiveness of ICIs.

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Comparison of a combination of chemotherapy and immune checkpoint inhibitors and immune checkpoint inhibitors alone for the treatment of advanced and metastatic non‐small cell lung cancer

Cited by 18 publications

References 33 publications

CCL7 recruits cDC1 to promote antitumor immunity and facilitate checkpoint immunotherapy to non-small cell lung cancer

CCL7 recruits cDC1 to promote antitumor immunity and facilitate checkpoint immunotherapy to non-small cell lung cancer

Epidermal Growth Factor Receptor (EGFR) Pathway, Yes-Associated Protein (YAP) and the Regulation of Programmed Death-Ligand 1 (PD-L1) in Non-Small Cell Lung Cancer (NSCLC)

The Effectiveness and Safety of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer Patients With Stage III/IV: A Multicenter Study

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