Chemotherapy In Non-small Cell Lung Cancer Research Articles

Cost-Effectiveness of Nivolumab Plus Ipilimumab With and Without Chemotherapy for Advanced Non-Small Cell Lung Cancer.

BackgroundFirst-line treatment with nivolumab plus ipilimumab (N+I) or nivolumab plus ipilimumab with two cycles of chemotherapy (N+I+chemotherapy) improve overall survival and progression-free survival for patients with metastatic non-small cell lung cancer (NSCLC), yet researchers have not concomitantly compared the cost-effectiveness of N+I and N+I+chemotherapy with chemotherapy alone.Materials and methodsUsing outcomes data from the CheckMate 227 and CheckMate 9LA phase 3 randomized trials, we developed a Markov model with lifetime horizon to compare the costs and effectiveness of N+I and N+I+chemotherapy versus chemotherapy from the U.S. health care sector perspective. Subgroup analysis by programmed death-ligand 1 (PD-L1) expression levels (≥1% and <1%) and probabilistic analysis were performed.ResultsThe incremental cost-effectiveness ratio (ICER) of N+I versus chemotherapy was $239,072 per QALY, and $838,198 per QALY for N+I+chemotherapy versus N+I. The ICER of N+I versus chemotherapy was $246,584 per QALY for patients with PD-L1 ≥ 1% and $185,620 per QALY for those with PD-L1 < 1%. In probabilistic analysis, N+I had a 2.6% probability of being cost-effective at a willingness-to-pay threshold of $150,000 per QALY. The probability was 0.4% for patients with PD-L1 ≥ 1% and 10.6% for patients with PD-L1 < 1%.ConclusionFirst-line N+I or N+I+chemotherapy for metastatic NSCLC was not cost-effective regardless of PD-L1 expression levels from the U.S. health care sector perspective.

Survival impact of treatment for chronic obstructive pulmonary disease in patients with advanced non-small-cell lung cancer

Chronic obstructive pulmonary disease (COPD) may coexist with lung cancer, but the impact on prognosis is uncertain. Moreover, it is unclear whether pharmacological treatment for COPD improves the patient’s prognosis. We retrospectively investigated patients with advanced non-small-cell lung cancer (NSCLC) who had received chemotherapy at Kyoto University Hospital. Coexisting COPD was diagnosed by spirometry, and the association between pharmacological treatment for COPD and overall survival (OS) was assessed. Of the 550 patients who underwent chemotherapy for advanced NSCLC between 2007 and 2014, 347 patients who underwent spirometry were analyzed. Coexisting COPD was revealed in 103 patients (COPD group). The median OS was shorter in the COPD group than the non-COPD group (10.6 vs. 16.8 months). Thirty-seven patients had received COPD treatment, and they had a significantly longer median OS than those without treatment (16.7 vs. 8.2 months). Multivariate Cox regression analysis confirmed the positive prognostic impact of COPD treatment. Additional validation analysis revealed similar results in patients treated with immune checkpoint inhibitors (ICIs). Coexisting COPD had a significant association with poor prognosis in advanced NSCLC patients if they did not have pharmacological treatment for COPD. Treatment for coexisting COPD has the potential to salvage the prognosis.

Molecular profiles of predictive biomarkers for platinum-based chemotherapy in Non-Small Cell Lung Cancer (NSCLC)

BackgroundNon-small cell lung cancer (NSCLC) is the principal subtype of lung cancer. Among all therapeutic options, platinum-based chemotherapy agents, especially Cisplatin, are still commonly used treatment for NSCLC patients. However, developing chemoresistance in NSCLC cells often gives rise to chemotherapy failure. Therefore, more studies are required to shed light on gene interaction and cellular pathways involved in initiating and developing resistance to platinum-based chemotherapy in NSCLC. Hence, it is urgent to find the key genes, microRNA (miRNAs), and potential molecular mechanisms implicated in chemoresistance and present markers to predict response to platinum-based chemotherapy in NSCLC patients. MethodsThe microarray datasets GSE6410, GSE7035, GSE14814, GSE26704, GSE73302 were downloaded from the Gene Expression Omnibus (GEO) database and were analyzed using R software. Functional and pathway enrichment analyses were performed using the Enrich R site. Then, the protein-protein interaction (PPI) network and hub genes were obtained using the Cytoscape software. Further, the miRSystem database was performed to predict the miRNAs regulating the hub genes. Moreover, Cytoscape software and the CytoHubba plugin were used to construct the miRNA-target interaction network and hub modules. Finally, the Kaplan–Meier curve was used to demonstrate the survival curves and assess the association of the genes signature with clinical outcomes. ResultsA total of 142 differentially expressed genes (DEGs) were found. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses present the p53 signaling pathway as the most significant pathway.Besides, from the top ten terms obtained of Biological Process, Molecular Function, and Cellular Component, the first ones, including cholesterol biosynthetic process, the extrinsic component of external side of plasma membrane, cytokine activity, were selected respectively. Based on the PPI network, the ten nodes with the highest degree were screened as hub genes. In addition, from the miRNA–target regulatory network in Cytoscape, ten hub nodes were found. Ultimately, according to Kaplan–Meier curve, BTG2 and TP53I3 with p-value <0.05 were associated with a better prognosis. ConclusionsIn the present study, DEGs, candidate miRNAs, and underlying mechanisms involved in chemoresistance were identified to suggest potential biomarkers to provide new clues for the prediction of response to platinum-based chemotherapy.

Research Progress and Challenges in the Treatment of Central Nervous System Metastasis of Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors and has high morbidity and mortality rates. Central nervous system (CNS) metastasis is one of the most frequent complications in patients with NSCLC and seriously affects the quality of life (QOL) and overall survival (OS) of patients, with a median OS of untreated patients of only 1–3 months. There are various treatment methods for NSCLC CNS metastasis, including surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy, which do not meet the requirements of patients in terms of improving OS and QOL. There are still many problems in the treatment of NSCLC CNS metastasis that need to be solved urgently. This review summarizes the research progress in the treatment of NSCLC CNS metastasis to provide a reference for clinical practice.

P03.01 Pathologic Response to Neoadjuvant PD-1 Inhibitors and Chemotherapy in Squamous Non-Small-Cell Lung Cancer

Several randomized studies have shown that the combination of programmed cell death 1 (PD-1) inhibitor and chemotherapy is efficacious as a treatment for advanced non-small-cell lung cancer (NSCLC), however, in the neoadjuvant setting, there is scarce evidence of the effectiveness and safety of the combinations in squamous NSCLC. We conducted a retrospective study to evaluate neoadjuvant PD-1 inhibitor plus chemotherapy in resectable squamous NSCLC.

Downregulation of LINC01296 suppresses non-small-cell lung cancer via targeting miR-143-3p/ATG2B.

The 5-year survival rate of lung cancer is one of the lowest among various malignant tumors. Long noncoding RNAs (lncRNAs), noncoding RNAs longer than 200 nucleotides, can function either as tumor suppressors or as oncogenes. The aim of this study is to investigate the function of lncRNA LINC01296 and its molecular mechanism in non-small-cell lung cancer (NSCLC). According to the Gene Expression Omnibus database, 10 differentially expressed lncRNAs in NSCLC cells and patient tissues are upregulated. LINC01296 is the one with the most significant overexpression. Knockdown of LINC01296 inhibits the growth and migration, arrests the cell cycle, and promotes the apoptosis of NSCLC cells. Knocking down LINC01296 in vivo suppresses tumor growth and metastasis. LINC01296 also acts as the sponge of miR-143-3p. Lowering the expression of LINC01296 leads to decreased expression of autophagy-related 2B (ATG2B), a target gene of miR-143-3p. Moreover, downregulation of LINC01296 promotes paclitaxel sensitivity in NSCLC. These results demonstrated that the LINC01296/miR-143-3p/ATG2B axis is crucial in promoting the development of NSCLC and paclitaxel resistance. Our study may provide new ideas for the further research of clinical chemotherapy of NSCLC in the near future.

MiR-519d-3p enhances the sensitivity of non-small-cell lung cancer to tyrosine kinase inhibitors.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. Tyrosine kinase inhibitors (TKIs) are currently the most effective chemotherapy for NSCLC. However, most cancer patients develop TKI resistance at tumor relapse stage. We firstly measured the expression change of miR-519d-3p in TKI resistance NSCLC cells. We then ectopically expressed miR-519-3p in TKI resistant cells to study its functional impact on cell proliferation, migration, invasion and cell sensitivity to gefitinib. The downstream target of miR-519-3p was identified by bioinformatics and validated in luciferase reporter assay and western blotting analysis. We also studied the reversing effect of the candidate target in NSCLC cells expressing miR-519d-3p. Lastly, we compared the miR-519d-3p level in NSCLC patients with good or poor response to gefitinib. miR-519d-3p level was downregulated in TKI resistant NSCLC cells. The restoration of miR-519d-3p in these NSCLC cells inhibited cell proliferation, invasion and migration; enhanced cell sensitivity to gefitinib. EPAS1 was identified and validated as downstream target of miR-519d-3p. Co-expressing EPAS1 antagonized the inhibitory effect of miR-519d-3p on NSCLC cells. MiR-519d-3p was downregulated in NSCLC patients with poor response to gefitinib. Targeting miR-519d-3p/EPAS1 axis may provide alternative treatment for TKI-resistant NSCLC.

Immune checkpoint inhibitors for first-line treatment of advanced non-small-cell lung cancer: A systematic review and network meta-analysis.

ObjectiveCurrently, several immune checkpoint inhibitors (ICIs) treatment for advanced non‐small‐cell lung cancer (NSCLC) have been investigated; their overall efficacy and safety remain unclear.MethodsWe searched electronic databases such as PubMed, EMBASE, and the Cochrane library. The randomized controlled trials (RCTs) that compared ICIs with or without chemotherapy to chemotherapy in advanced NSCLC. We collected and compaired thier parameters, including overall survival (OS), progression‐free survival (PFS), objective response rate (ORR), and treatment‐related adverse events (TRAEs) of grade ≥3.ResultsA total of 15 RCTs involving 8869 patients with NSCLC were included. Pembrolizumab plus platinum‐based chemotherapy had higher OS and PFS than platinum‐based chemotherapy (hazard ratio [HR] 0.55, 95% CI 0.46–0.67; HR 0.54, 95% CI 0.41–0.70, respectively). Pembrolizumab plus platinum‐based chemotherapy had higher ranked ORR than platinum‐based chemotherapy (odds ratio [OR] 2.92, 95% CI 1.99–4.22). In terms of OS, atezolizumab, pembrolizumab plus platinum‐based chemotherapy, and nivolumab plus ipilimumab ranked as the best treatments for patients with programmed death‐ligand 1 (PD‐L1) expression levels of ≥50%, 1–49%, and <1%, respectively. In terms of PFS, pembrolizumab plus platinum‐based chemotherapy ranked as the best treatment for patients with any PD‐L1 expression levels. However, ipilimumab plus platinum‐based chemotherapy, nivolumab plus platinum‐based chemotherapy, and atezolizumab plus platinum‐based chemotherapy have higher TRAEs of grade ≥3 than platinum‐based chemotherapy.ConclusionsPembrolizumab plus platinum‐based chemotherapy prevailed in rank in OS, PFS, and ORR benefit. The TRAEs of pembrolizumab plus platinum‐based chemotherapy were more than ICI monotherapy and chemotherapy.

1332P A randomized phase II trial of standard versus low-dose nab-paclitaxel for previously treated advanced non-small cell lung cancer (JMTO LC14-01)

Nanoparticle albumin-bound (nab) paclitaxel is an active agent for non–small cell lung cancer (NSCLC). Nab-paclitaxel proved to be noninferior to docetaxel with regard to overall survival (OS), having showcased improved progression-free survival (PFS) and overall response rate (ORR) in patients with previously treated advanced NSCLC, according to findings from the phase III trial in Japan (J-AXEL study, 2021). In chemotherapy for advanced NSCLC, it is expected that administration of the optimal dose for as long as possible will lead to improvement of prognosis rather than administration of the maximum tolerated dose for a short period of time.

1151MO Pathological response is an independent factor of overall survival and disease-free survival after neoadjuvant durvalumab in resectable non-small cell lung cancer (NSCLC) in the IFCT-1601 IONESCO phase II trial

Major pathological response after neoadjuvant cisplatin-based chemotherapy for early-stage NSCLC has been shown to predict survival. This has not been demonstrated for neoadjuvant immune checkpoint inhibitors. In IONESCO multicenter phase II trial, 3 cycles of durvalumab were administered in stage IB>4cm–IIIA, non N2 resectable NSCLC (TNM 8th edition) before surgery. We report here the updated analysis on disease-free survival (DFS) and overall survival (OS) and their association with residual viable tumor cells (RVT). Tissue specimens from patients who underwent neoadjuvant durvalumab and complete surgical resection were retrospectively evaluated by two pathologists blinded to patient outcomes. Specimens were reviewed for the degree of pathologic response i.e. % of RVT in the primary tumor and in any involved lymph nodes. The relationship between % of RVT as a continuous variable and outcomes (OS and DFS) was analyzed using a Cox regression model including patient characteristics (age, gender, PS, smoking status), histology, PD-L1 tumor proportion score (TPS), stage and surgical procedure. 50 pts were included. 46 were eligible and received durvalumab, 43 operated, 67.4% males, median age, 61 yr; all ECOG PS 0-1; 98% (ex-)smokers; 23 adenocarcinoma, 19 squamous; clinical stages IB/IIA/IIB/IIIA = 5/13/27/1; 15 TPS ≥1%. Median % of RVT was 36.11. Median OS and DFS were not reached; 18-m OS: 89.1% [95% CI: 75.8-95.3] 18-m DFS: 73.7% [95% CI: 58.4-84.1]. In the multivariate prognostic analysis, for increasing value of % of RVT, OS and DFS were poorer (HR [95%CI]: 1.05 [1.00-1.10] p=0.04 and 1.06 [1.01-1.11] p=0.02, respectively). The IFCT-1601 IONESCO trial showed for the first time that the extent of pathological response to a neoadjuvant immune checkpoint inhibitor is an independent prognostic factor of OS and DFS in NSCLC.

1176P Neoadjuvant PD-1 inhibitor (toripalimab) plus chemotherapy in patients with potentially resectable NSCLC: An open-label, single-arm, phase II trial

Previous studies showed neoadjuvant therapy with a programmed cell death protein 1 (PD-1) inhibitor could benefit patients (pts) with resectable non-small-cell lung cancer (NSCLC). On this basis, we initiated a phase II clinical trial to report the safety and effectiveness of neoadjuvant Toripalimab plus chemotherapy in local advanced NSCLC.

EGFR exon 20 Insertion NSCLC and Response to Platinum-Based Chemotherapy

IntroductionIn classical EGFR mutant non-small-cell lung cancer (NSCLC), EGFR tyrosine kinase inhibitor (TKI) therapy yields better outcomes than platinum-based chemotherapy. However, EGFR exon 20 insertion (ex20ins) NSCLC is relatively resistant to currently available EGFR TKIs. Though platinum-based chemotherapy is the frontline standard of care for EGFR ex20ins NSCLC, its efficacy is not fully described. Study DesignA retrospective, single-center, case series MethodsPatients were identified through an electronic research database at a single institution and included if they had advanced EGFR ex20ins NSCLC, received platinum-based chemotherapy for metastatic disease, and had scans evaluable for response. Each patient's demographics, tumor characteristics, and clinical course were recorded. Treatment response was evaluated using RECIST v1.1 criteria, and the PFS was calculated by the Kaplan-Meier method. ResultsAmong 27 patients identified with EGFR ex20ins NSCLC at our institution, 18 (67%) received platinum-based chemotherapy for metastatic disease and had scans evaluable for response. These patients received platinum-based chemotherapy in the first-line (N = 17, 94%) and second-line settings (N = 1, 6%). The objective response rate (ORR) to platinum-based chemotherapy was 39% (7 of 18 patients; 95% confidence interval [CI] 16-61). The median PFS with platinum-based chemotherapy was 7.1 months (95% CI, 6.3 -13.7), and the median overall survival was 3.2 years (95% CI, 1.92 – NR). ConclusionsThe efficacy of platinum-based chemotherapy in EGFR ex20ins NSCLC is similar to that expected for TKI sensitive EGFR mutant NSCLC. Novel agents designed to specifically target ex20ins mutant EGFR should additionally improve outcomes.

Abstract 374: NGS based profiling of homologous recombination genes to predict response to platinum-based chemotherapy in NSCLC

Abstract Background: In the era of precision medicine, better response of anti-tumor therapies attribute to detection of specific molecular markers. However, up to the present no validated biomarker for platinum-based chemotherapy could be used in clinic. Next-generation sequencing (NGS) technology has been applied for non-small cell lung cancer (NSCLC) molecular typing for years. Whether analysis of homologous recombination (HR) gene mutations based on NGS results could predict the efficiency of platinum-based therapy in NSCLC is still obscure. Methods: NGS has been performed for screening homologous recombination (HR) gene mutations, as well as common driver genes in NSCLC, with tumor samples. Advanced or metastatic NSCLC patients receiving platinum-based chemotherapy were included for efficacy analysis. Results: 129 patients with HR genes information were included for analysis. Among the 129 patients, 55 patients were received platinum-based chemotherapy. The efficiency results showed the objective response rates (ORR) of patients with BRCA1/2 and without BRCA1/2 mutations were 71.4% and 31.3%; and the median progression free survival (PFS) were 7.5 and 5.6 months(p=0.161), respectively. The ORR of patients with and without HR genes mutations were 57.9% and 25.0%; and the median PFS were 8.0 and 5.3 months (p=0.039), respectively. Conclusions: NGS based profiling of BRCA1/2 and other gene mutations in HR pathways have a promising predictive value for efficacy of platinum-based chemotherapy in advance and metastatic NSCLC. Citation Format: Linlin Zhang, Xin Wang, Hui Song, Fanlu Meng, Guowei Yu, Diansheng Zhong. NGS based profiling of homologous recombination genes to predict response to platinum-based chemotherapy in NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 374.

Abstract SY13-03: Neoadjuvant immunotherapy for operable non-small cell lung cancer: Lessons learned and current challenges

Abstract SY13-03: Neoadjuvant immunotherapy for operable non-small cell lung cancer: Lessons learned and current challenges

Immune Checkpoint and Anti-Angiogenic Antibodies for the Treatment of Non-Small Cell Lung Cancer in the European Union and United States.

Several types of antibodies (Abs) are currently used in non-small cell lung cancer (NSCLC). Anti-angiogenic and immune checkpoint inhibitor (ICI) Abs are the most frequent treatments used alone or with chemotherapy in metastatic NSCLC, for the front line and beyond. Considering the many therapeutic options for locally advanced and metastatic lung cancer and differences in use according to geographic area, we present here a comprehensive review of the marketed ICI and anti-angiogenic Abs approved in the European Union (EU) and the US to treat locally advanced and metastatic NSCLC patients. We briefly describe the different molecules and their development in thoracic oncology and compare pharmacokinetic data, processing decision algorithms and marketing authorizations by the EMA and US Food and Drug Administration (FDA).

Polymorphisms in EGFR Gene Predict Clinical Outcome in Unresectable Non-Small Cell Lung Cancer Treated with Radiotherapy and Platinum-Based Chemoradiotherapy.

For non-small cell lung cancer (NSCLC), radiotherapy (RT) and platinum-based chemotherapy (CHT) are among the main treatment options. On the other hand, radioresistance and cytotoxic drug resistance are common causes of failure. The epidermal growth factor receptor (EGFR) plays an important role in radioresponse and therapy resistance. We hypothesized that single nucleotide polymorphisms (SNPs) in the EGFR gene might affect individual sensitivity to these treatments, and thus, therapy outcome and prognosis. The association between functional EGFR SNPs and overall (OS), locoregional recurrence-free (LFRS), and metastasis-free (MFS) survival was examined in 436 patients with unresectable NSCLC receiving RT and platinum-based CHTRT. In a multivariate analysis, the rs712830 CC homozygotes showed reduced OS in the whole group (p = 0.039) and in the curative treatment subset (p = 0.047). The rs712829 TT genotype was strongly associated with decreased LRFS (p = 0.006), and the T-C haplotype was a risk factor for locoregional recurrence in our patients (p = 0.003). The rs2227983 GG alone and in combination with rs712829 T was an indicator of unfavorable LRFS (p = 0.028 and 0.002, respectively). Moreover, significant independent effects of these SNPs on OS, LRFS, and MFS were observed. Our results demonstrate that inherited EGFR gene variants may predict clinical outcomes in NSCLC treated with DNA damage-inducing therapy.

KRYSTAL-12: A randomized phase 3 study of adagrasib (MRTX849) versus docetaxel in patients (pts) with previously treated non-small-cell lung cancer (NSCLC) with KRASG12C mutation.

TPS9129 Background: Despite significant advances in chemotherapy and immunotherapy for advanced NSCLC, the majority of pts ultimately develop progressive disease associated with poor outcomes. KRAS is a key mediator of the RAS/MAPK signaling cascade that promotes cell growth and proliferation. KRASG12C mutations occur in 14% of NSCLC (adenocarcinoma), and mutations in KRAS are associated with a poor prognosis. Although KRAS has historically been undruggable, recent research into the development of agents that specifically bind mutant KRAS has led to the development of direct inhibitors of KRASG12C. Adagrasib, an investigational agent, is a potent, covalent inhibitor of KRASG12C that irreversibly and selectively binds to and locks KRASG12C in its inactive state. Adagrasib was optimized for favorable pharmacokinetic (PK) properties, including oral bioavailability, long half-life (̃24 h), and extensive tissue distribution. Initial results have demonstrated encouraging antitumor activity and tolerability of adagrasib monotherapy in pts with NSCLC harboring a KRASG12C mutation. Methods: KRYSTAL-12 is a multicenter, randomized Phase 3 study evaluating the efficacy of adagrasib (600 mg BID) vs docetaxel in pts with advanced NSCLC harboring a KRASG12C mutation who have progressed during or after treatment with a platinum-based regimen and an immune checkpoint inhibitor. The study is designed to demonstrate improvement in the dual primary endpoints of progression-free survival (PFS) and overall survival (OS). Secondary endpoints include safety, objective response rate (ORR) per RECIST 1.1, duration of response (DOR), plasma PK parameters of adagrasib, and patient-reported outcomes (PROs). The study will also explore correlations between gene alterations (at baseline and upon development of treatment resistance) and efficacy. Approximately 450 patients will be randomized in a 2:1 ratio to receive adagrasib or docetaxel and will be stratified by region (United States/Canada vs other countries) and sequential vs concurrent administration of prior platinum-based chemotherapy and anti–PD-1/PD-L1 antibody. The planned sample size is sufficiently powered for the hypothesized treatment effect of the endpoints. Pts will receive study treatment until disease progression, unacceptable adverse events, investigator decision to terminate treatment, or patient withdrawal. This study is currently enrolling and will be open at sites in the United States, Europe, and Asia. Clinical trial information: NCT04685135.

Correlation between MTHFR 677C &gt; T polymorphism and response of pemetrexed-based chemotherapy in advanced NSCLC: A meta-analysis

Abstract Objective The aim of this study was to investigate the correlation between MTHFR 677C &gt; T polymorphism and response of pemetrexed-based chemotherapy in advanced non-small-cell lung cancer (NSCLC) by pooling the open published relevant studies. Methods Clinical studies associated with MTHFR 677C &gt; T polymorphism and response of pemetrexed-based chemotherapy in advanced NSCLC were systematically searched in databases of Pubmed, Embase, Cochrance Library, China national knowledge infrastructure (CNKI) and Wanfang. The correlation was expressed by odds ratio (OR) and corresponding 95% confidence interval (95% CI). The publication bias of the included studies was evaluated through Begg’s funnel plot and Egger’s line regression test. Results Ten prospective clinical studies relevant to MTHFR 677C &gt; T polymorphism and response of pemetrexed-based chemotherapy in NSCLC were included in the present meta-analysis. The pooled results indicated that the partial response in NSCLC patients with TT or CT genotype was inferior to CC genotype in a dominant gene model (TT + CT vs CC) (OR = 0.16, 95% CI: 0.06–0.41, P = 0.001). NSCLC cases with T genotype were inferior to C genotype in the objective response rate treated with pemetrexed-based chemotherapy for dominant (OR = 0.28, 95% CI: 0.18–0.45, P = 0.001), recessive (OR = 0.43, 95% CI: 0.19–0.94, P = 0.03) and homozygous models (OR = 0.30, 95% CI: 0.13–0.67, P = 0.003). However, there was no statistical difference in disease control rate, progressive disease between different genotypes of different gene models (P all &gt; 0.05). Conclusion The pemetrexed-based chemotherapy response was decreased in NSCLC cases with T genotype, which can be applied as a potential pemetrexed-based chemotherapy response marker.

Van der Waals force-driven indomethacin-ss-paclitaxel nanodrugs for reversing multidrug resistance and enhancing NSCLC therapy

The high expression of multidrug resistance-associated protein 1 (MRP1) in cancer cells caused serious multidrug resistance (MDR), which limited the effectiveness of paclitaxel (PTX) in non-small cell lung cancer (NSCLC) chemotherapy. Indomethacin (IND), a kind of non-steroidal anti-inflammatory drugs (NSAIDs), which has been confirmed to be a potential MRP1 inhibitor. Taking into account the advantages of old drugs without extra controversial biosafety issue, in this manuscript, the disulfide bond (-S-S-) was employed for connecting IND and PTX to construct conjugate IND-S-S-PTX, which was further self-assembled and formed nanodrug (IND-S-S-PTX NPs). The particle size of IND-S-S-PTX NPs was ~160 nm with a narrow PDI value of 0.099, which distributed well in water and also exhibited a stable characteristic. Moreover, due to the existence of disulfide bond, the NPs were sensitive to the high level of glutathione (GSH) in tumor microenvironment. Molecular dynamics (MD) simulation presented the process of self-assembly in detail. Density functional theory (DFT) calculations revealed that the main driving force in self-assembly process was originated from the van der waals force. In addition, this carrier-free nano drug delivery systems (nDDs) could reverse the MDR by downregulating the expression of MRP1 protein in A549/taxol.

Single or combined immune checkpoint inhibitors compared to first-line platinum-based chemotherapy with or without bevacizumab for people with advanced non-small cell lung cancer.

Single or combined immune checkpoint inhibitors compared to first-line platinum-based chemotherapy with or without bevacizumab for people with advanced non-small cell lung cancer.