Immune checkpoint inhibitors are superior to docetaxel as second-line therapy for patients with non-small cell lung carcinoma
01 May 2018-CA: A Cancer Journal for Clinicians (American Cancer Society)-Vol. 68, Iss: 3, pp 178-179
TL;DR: A new study confirms the value of epidermal growth factor receptor (EGFR) mutation status when choosing immune checkpoint inhibitors versus docetaxel chemotherapy as a second-line treatment of patients with advanced nonsmall cell lung carcinoma.
Abstract: A new study confirms the value of epidermal growth factor receptor (EGFR) mutation status when choosing immune checkpoint inhibitors versus docetaxel chemotherapy as a second-line treatment of patients with advanced nonsmall cell lung carcinoma (NSCLC). The meta-analysis, which appears in JAMA Oncology, includes data from 5 clinical trials with a cumulative total of 3025 patients with advanced NSCLC (JAMA Oncol. 2018;4:210-216).
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TL;DR: A deeper understanding of the lncRNA-related ceRNA network in NSCLC is provided and some genes may be new target to treat forNSCLC patients.
Abstract: Background Non-small cell lung cancer (NSCLC) is the most common cancer and the pathogenesis remain unclear. According to the competing endogenous RNA (ceRNA) theory, long noncoding RNA (lncRNA) have a competition with mRNAs for the connecting with miRNAs that affecting the level of mRNA. In this work, the ceRNA network and the important genes to predict the survival prognosis were explored. Methods In the study, we recognized differently expressed genes (mRNAs, lncRNAs and miRNAs) between NSCLC and normal tissues from The Cancer Genome Atlas database (fold change >2, P<0.01) using edgeR. Then, the interaction between lncRNA and miRNA or mRNA and miRNA was explored by miRcode, miRDB, TargetScan, and miRanda. Furthermore, the functions and KEGG pathway were analyzed with DAVID and KOBAS. The connections of these mRNAs were explored by STRING online database. The relation between genes in the network and survival time were further explored by survival package in R. Results By bioinformatics tools, we explored 155 lncRNAs, 30 miRNAs and 68 mRNAs and constructed ceRNA network. The functions and KEGG pathway of 68 mRNAs were further analyzed. AQP2, EGF, SLC12A1, TRPV5 and AVPR2 was in the center of network and may play key roles in the development of NSCLC. And mRNA (CCNB1, COL1A1, E2F7, EGLN3, FOXG1 and PFKP), miRNA (miR-31, miR-144 and miR-192) and lncRNA (AC080129.1, AC100791.1, AL163952.1, AP000525.1, AP003064.2, C2orf48, C10orf91, FGF12-AS2, HOTAIR, LINC00518, LNX1-AS1, MED4-AS1, MIG31HG, MUC2, TTTY16 and UCA1) were closely related with overall survival (OS). Conclusions In summary, the present study provides a deeper understanding of the lncRNA-related ceRNA network in NSCLC and some genes may be new target to treat for NSCLC patients.
41 citations
Cites background from "Immune checkpoint inhibitors are su..."
...Therefore, the mechanisms of this disease are urgently needed (21)....
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TL;DR: The comparative efficacy and safety of ICI‐chemotherapy versus ICi‐monotherapy in advanced NSCLC is estimated.
Abstract: Background Lung cancer is the leading cause of cancer-related deaths worldwide and the prognosis remains poor. The recent introduction of the immune checkpoint inhibitor (ICI), or plus chemotherapy, both resulted in the survival benefit for patients with advanced non-small-cell lung cancer (NSCLC), but it remains unanswered which is superior. The current study aimed to estimate the comparative efficacy and safety of ICI-chemotherapy versus ICI-monotherapy in advanced NSCLC. Methods Studies were identified by searching PubMed, Embase, and Cochrane library. The randomized controlled trials (RCTs) that ICI monotherapy or ICI plus chemotherapy compared with chemotherapy in NSCLC were included with available primary endpoints of progression-free survival (PFS), overall survival (OS), objective response rate, or treatment-related adverse events. A fixed-effect or random-effects model was adopted depending on between-study heterogeneity. Results A total of 20 RCTs involving 12,025 patients with NSCLC were included. Both ICI-monotherapy and ICI-chemotherapy resulted in significantly prolonged survival compared to chemotherapy and the former led to significantly longer PFS. The magnitude of survival benefits appeared to be greatest among those treated with pembrolizumab plus platinum-based chemotherapy (OS, 0.56; PFS, 0.54). Additionally, OS and PFS advantages of ICI therapies were observed in patients with NSCLC with low or high programmed cell death 1 ligand 1 (PD-L1) expression level, but not in intermediate PD-L1 TPS. Conclusions Pembrolizumab plus platinum-based chemotherapy was recommended as the optimal first-line therapy for advanced patients with NSCLC. Additionally, PD-L1 alone is not recommended as an adequate molecular biomarker to identify eligible patients for routine clinical practice in immunotherapy.
39 citations
Cites background from "Immune checkpoint inhibitors are su..."
...On the other hand, new agents, such as docetaxel (DOC), can significantly improve survival benefits comparing with supportive care, but at the expense of a higher risk of adverse events (Fillon, 2018)....
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...In general, treatment for patients with squamous NSCLC has been an area of unmet need with the little improvement of therapeutic effects since the approval of DOC in 1999 (Fillon, 2018; Melosky et al., 2016)....
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TL;DR: It is reported that increased expression levels of miR-134-5p and decreased levels of disabled-2 (DAB2) were significantly correlated with recurrence in stage I LUAD patients, and it is demonstrated that DAB2 is a target of miDAB2 and that miR/5p stimulates chemoresistance and metastasis through DAB1 in LUAD.
Abstract: Despite surgery and adjuvant therapy, early-stage lung adenocarcinoma (LUAD) treatment often fails due to local or metastatic recurrence. However, the mechanism is largely unknown. Here, we report that increased expression levels of miR-134-5p and decreased levels of disabled-2 (DAB2) were significantly correlated with recurrence in stage I LUAD patients. Our data show that miR-134-5p overexpression or DAB2 silencing strongly stimulated LUAD cell metastasis and chemoresistance. In contrast, inhibition of miR-134-5p or overexpression of DAB2 strongly suppressed LUAD cell metastasis and overcame the insensitivity of chemoresistant LUAD cells to chemotherapy. In addition, we demonstrated that DAB2 is a target of miR-134-5p and that miR-134-5p stimulates chemoresistance and metastasis through DAB2 in LUAD. Taken together, these findings suggest that miR-134-5p and its target gene DAB2 have potential as a biomarker for predicting recurrence in stage I LUAD patients. Additionally, miR-134-5p inhibition or DAB2 restoration may be a novel strategy for inhibiting LUAD metastasis and overcoming LUAD cell resistance to chemotherapy.
27 citations
TL;DR: It is not necessary to pick AYA cancer patients out when considering suicide risk of cancer patients, and earlier cancer stage and longer survival time within 5 years are similar prevalent risk factors for both AYA group patients and all-age patients.
Abstract: Background: Many researchers have studied suicide risk factors of patients with one specific cancer. But there is no comprehensive study to compare suicide issues between adolescents and young adult (AYA) group and all-age groups in a pan-cancer view.
Methods: Patients diagnosed with 20 solid malignancies were identified from SEER database. Multivariable logistic regression was operated to find out risk factors of suicide.
Results: Male sex has less impact on AYA than all-age patients (OR 2.72, 95% CI: 2.23–3.31, P vs . OR 4.64, 95% CI: 4.37–4.94, P vs . OR 3.40, 95% CI: 3.02–3.84, P vs . OR 1.39, 95% CI: 1.33–1.46, P vs . OR 1.76, 95% CI: 1.61–1.92; P vs . 1.24, P Conclusions: Male sex, white race and unmarried status, earlier cancer stage and longer survival time within 5 years are similar prevalent risk factors for both AYA group patients and all-age patients. It is not necessary to pick AYA cancer patients out when considering suicide risk of cancer patients.
14 citations
TL;DR: The mechanisms affecting the activity of NK cells were reviewed, and the therapeutic potential of different basic NK cell strategies in tumor therapy was focused on.
Abstract: NK cells are lymphocytes with antitumor properties and can directly lyse tumor cells in a non-MHC-restricted manner. However, the tumor microenvironment affects the immune function of NK cells, which leads to immune evasion. This may be related to the pathogenesis of some diseases. Therefore, great efforts have been made to improve the immunotherapy effect of natural killer cells. NK cells from different sources can meet different clinical needs, in order to minimize the inhibition of NK cells and maximize the response potential of NK cells, for example, modification of NK cells can increase the number of NK cells in tumor target area, change the direction of NK cells, and improve their targeting ability to malignant cells. Checkpoint blocking is also a promising strategy for NK cells to kill tumor cells. Combination therapy is another strategy for improving antitumor ability, especially in combination with oncolytic viruses and nanomaterials. In this paper, the mechanisms affecting the activity of NK cells were reviewed, and the therapeutic potential of different basic NK cell strategies in tumor therapy was focused on. The main strategies for improving the immune function of NK cells were described, and some new strategies were proposed.
10 citations