Efficacy of pemetrexed plus platinum doublet chemotherapy as first-line treatment for advanced nonsquamous non-small-cell-lung cancer: a systematic review and meta-analysis

Xiao, Huaiqing; Tian, Rong-Hua; Zhang, Zhihao; Du, Kun; Ni, Yiming

doi:10.2147/ott.s96160

Cited by 15 publications

(6 citation statements)

References 25 publications

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“…Activated ERK/AKT signaling can contribute to drug resistance in cancer cells 18 . Given the suppressive role of miR-24, miR-27b and miR-125a-5p on ERKs/AKT activation, we examined the effect after overexpression of these miRNAs in response to pemetrexed alone or as platinum doublet, commonly used as first line chemotherapy in patients with advanced NSCLC 19 or TRAIL. As confirmed by proliferation assay, A549 cells transfected with miR-23b, miR-24, miR-27b or miR-125a-5p were significantly less viable after cisplatin, pemetrexed (or the combination cisplatin/pemetrexed) and after TRAIL treatment compared to control cells ( p < 0.001, Fig.…”

Section: Resultsmentioning

confidence: 99%

PDGFR-modulated miR-23b cluster and miR-125a-5p suppress lung tumorigenesis by targeting multiple components of KRAS and NF-kB pathways

Naidu

Shi

Magee

et al. 2017

Sci Rep

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In NSCLC alterations in PDGF receptors are markers of worst prognosis and efficient targeting of these receptors is yet to be achieved. In this study, we explored PDGFR-regulated microRNAs demonstrating that miR-23b cluster and miR-125a-5p are downregulated by increased expression of PDGFR-α or PDGFR-β in NSCLC cells. Mechanistically, the expression of these microRNAs is positively regulated by p53 and negatively modulated by NF-kB p65. Forced expression of miR-23b cluster or miR-125a-5p enhanced drug sensitivity and suppressed invasiveness of NSCLC cells by silencing several genes involved in oncogenic KRAS and NF-kB pathways, including SOS1, GRB2, IQGAP1, RALA, RAF-1, IKKβ, AKT2, ERK2 and KRAS itself. Of note, an inverse correlation between miR-23b cluster, miR-125a-5p and respective target genes was also found in vivo in a large dataset of lung adenocarcinoma samples. Furthermore, in vivo delivery of miR-23b cluster or miR-125a-5p significantly repressed tumour growth in a highly aggressive NSCLC circulating tumour cell (CTC) patient derived explant (CDX) mouse model. In conclusion, our finding sheds light on the PDGFR signaling and endorses the possibility to employ miR-23b cluster and miR-125a-5p as therapeutic tools to silence simultaneously a range of redundant pathways and main effectors of tumorigenesis in NSCLC.

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Section: Resultsmentioning

confidence: 99%

PDGFR-modulated miR-23b cluster and miR-125a-5p suppress lung tumorigenesis by targeting multiple components of KRAS and NF-kB pathways

Naidu

Shi

Magee

et al. 2017

Sci Rep

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“…The subsequent NEJ002 and WJTOG3405 trials, which included only patients harboring EGFR mutations, further confirmed that gefitinib is superior to (pemetrexed-free) chemotherapy in terms of PFS (HR 0.30, 95% CI 0.22-0.41 in the NEJ002 trial, and HR 0.49, 95% CI 0.33-0.71 in the WJTOG3405 trial) in patients harboring EGFR mutations [ 25 – 27 ]. One meta-analysis reported that the HR of PFS for pemetrexed plus platinum doublet chemotherapy relative to platinum plus another first-line chemotherapy agent as a first-line treatment for advanced non-squamous NSCLC patients was 0.90 (95% CI 0.80–1.01) [ 28 ].…”

Section: Methodsmentioning

confidence: 99%

Cost-effectiveness of gefitinib, icotinib, and pemetrexed-based chemotherapy as first-line treatments for advanced non-small cell lung cancer in China

Lü

Ding

et al. 2016

Oncotarget

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Tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR) are becoming the standard treatment option for patients with advanced non-small cell lung cancer (NSCLC) harboring an EGFR mutation, but the economic impact of this practice is unclear, especially in a health resource-limited setting. A decision-analytic model was developed to simulate 21-day patient transitions in a 10-year time horizon. The health and economic outcomes of four first-line strategies (pemetrexed plus cisplatin [PC] alone, PC followed by maintenance with pemetrexed, or initial treatment with gefitinib or icotinib) among patients harboring EGFR mutations were estimated and assessed via indirect comparisons. Costs in the Chinese setting were estimated. The primary outcome was the incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed. The icotinib strategy resulted in greater health benefits than the other three strategies in NSCLC patients harboring EGFR mutations. Relative to PC alone, PC followed by pemetrexed maintenance, gefitinib and icotinib resulted in ICERs of $104,657, $28,485 and $19,809 per quality-adjusted life-year gained, respectively. The cost of pemetrexed, the EGFR mutation prevalence and the utility of progression-free survival were factors that had a considerable impact on the model outcomes. When the icotinib Patient Assistance Program was available, the economic outcome of icotinib was more favorable. These results indicate that gene-guided therapy with icotinib might be a more cost-effective treatment option than traditional chemotherapy.

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“…Prior to the approval of immunotherapies, traditional first-line treatment for advanced and metastatic NSCLC was combination chemotherapy (CT), often comprising platinum alkylating agents in combination with taxanes [6]. CT agents that inhibit DNA synthesis such as pemetrexed, a multitargeted antifolate antagonist of pyrimidine and purine biosynthesis, have been shown to be combinable with platinumbased CT for adenocarcinoma NSCLC [7][8][9][10][11]. In the past decade, immunotherapies have improved clinical outcomes for biomarker-selected patients, and are now recommended in combination with platinum doublet CT in the standard management of advanced stage NSCLC [7,8,[12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Veliparib and nivolumab in combination with platinum doublet chemotherapy in patients with metastatic or advanced non-small cell lung cancer: A phase 1 dose escalation study

et al. 2021

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Both combinations of the PARP inhibitor veliparib plus platinum doublet chemotherapy (CT), and the programmed death receptor-1 (PD-1) inhibitor nivolumab plus CT have demonstrated encouraging efficacy for treatment of non-small cell lung cancer (NSCLC). This phase 1 dose-escalation study (NCT02944396) evaluated the quadruple combination of veliparib with nivolumab and doublet CT in patients with unresectable advanced/ metastatic NSCLC. Materials and methods: Patients were enrolled into five dosing cohorts: patients received veliparib 120 mg twice daily (BID) combined with nivolumab 360 mg, carboplatin AUC 6 mg/mL•min, and paclitaxel 200 mg/m 2 (C/ PAC) or veliparib 80/120/200/240 mg BID in combination with nivolumab 360 mg, carboplatin AUC 6 mg/ mL•min, and pemetrexed 500 mg/m 2 (C/PEM). Primary objective was to identify the recommended phase 2 dose (RP2D) of veliparib + nivolumab + CT. Safety, tolerability, and efficacy of this combination were also assessed. Results: Twenty-five patients were enrolled: 6 patients received veliparib 120 mg BID + nivolumab + C/PAC and 19 received veliparib (80-240 mg BID) + nivolumab + C/PEM. No dose-limiting toxicities were reported, and the RP2Ds were veliparib 120 mg BID + nivolumab + C/PAC, and veliparib 240 mg BID + nivolumab + C/PEM. The most common any-grade adverse events (AEs) were fatigue (56%), nausea (52%), and anemia (48%). Grade 3/4 AEs included anemia (32%) and neutropenia (24%), and the most frequent serious AE was malignant neoplasm progression (12%). Veliparib exhibited approximately dose proportional kinetics in the dose range Abbreviations: AUC 0-x , area under the plasma concentration-time curve from time 0 to x hour post dose concentration; AUC t , area under the plasma concentrationtime curve from time 0 to the last measurable concentration; AUC ∞ , area under the plasma concentration-time curve from time 0 to time infinity; AE, adverse event; AUC, target area under the concentration time curve;

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Efficacy of pemetrexed plus platinum doublet chemotherapy as first-line treatment for advanced nonsquamous non-small-cell-lung cancer: a systematic review and meta-analysis

Cited by 15 publications

References 25 publications

PDGFR-modulated miR-23b cluster and miR-125a-5p suppress lung tumorigenesis by targeting multiple components of KRAS and NF-kB pathways

PDGFR-modulated miR-23b cluster and miR-125a-5p suppress lung tumorigenesis by targeting multiple components of KRAS and NF-kB pathways

Cost-effectiveness of gefitinib, icotinib, and pemetrexed-based chemotherapy as first-line treatments for advanced non-small cell lung cancer in China

Veliparib and nivolumab in combination with platinum doublet chemotherapy in patients with metastatic or advanced non-small cell lung cancer: A phase 1 dose escalation study

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