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This was a single-arm, multicenter phase 2 clinical trial (ChiCTR1900021726) involving advanced squamous non-small cell lung cancer (sq-NSCLC) patients undergoing 2 cycles of nab-paclitaxel/carboplatin and sintilimab (anti-PD-1), followed by sintilimab maintenance therapy. The median progression-free survival (PFS) was 11.4 months (95% CI: 6.7-18.1), which met the pre-specified primary endpoint. Secondary endpoints included objective response rate reaching 70.5% and a disease control rate of 93.2%, with a median duration of response of 13.6 months [95% CI: 7.0-not evaluable (NE)]. The median overall survival was 27.2 months (95% CI: 20.2-NE) with treatment-related adverse events grades ≥3 occurring in 10.9% of patients. Predefined exploratory endpoints comprised relationships between biomarkers and treatment efficacy, and the association between circulating tumor DNA (ctDNA) dynamics and PFS. Biomarker analysis revealed that the breast cancer gene 2, BMP/Retinoic Acid Inducible Neural Specific 3, F-box/WD repeat-containing protein 7, tyrosine-protein kinase KIT and retinoblastoma 1 abnormalities led to shorter PFS, while ctDNA negative at baseline or clearance at 2 cycles of treatment was associated with longer PFS (18.1 vs. 4.3 months). Taken together, sintilimab in combination with 2 cycles of nab-paclitaxel/carboplatin treatment produced encouraging PFS and better tolerability as first-line treatment for advanced sq-NSCLC.
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Anticuerpos Monoclonales Humanizados , Carcinoma de Pulmón de Células no Pequeñas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/uso terapéutico , Carboplatino/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genéticaRESUMEN
In recent years, notable headway has been made in augmenting supercapacitor functioning through employment of pioneering components, exceptional nanostructures and additional investigation of electrolytes. Nonetheless, achieving superior performance with straightforward techniques remains a significant hurdle. In order to surmount this, an experimental three-dimensional nanospherical pore structure (TPB-20@Ni(OH)2) was designed and prepared. TPB-1 was obtained through carbonisation and activation. TPB-20@Ni(OH)2nanoparticles were synthesized using TPB-1 as the carbon source and nickel chloride hexahydrate as the nickel source. Furthermore, the TPB-20@Ni(OH)2//AC supercapacitor displayed an impressive energy density of 22.1 Wh kg-1. The TPB-20@Ni(OH)2composites exhibited a specific capacity of 978 F-1, which is noteworthy. The exceptional output exhibited by the TPB-20@Ni(OH)2composite derives from its innovative structure, presenting an extensive specific surface area of 237.4 m2g-1and porosity of roughly 4.0 nm. Following 20 000 cycles (at a current density of 1 A g-1), asymmetric supercapacitors assembled from TPB-20@Ni(OH)2//AC retained 80.0% of its initial specific electrostatic capacity, indicating superior electrochemical stability and high electrochemical reversibility.
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BACKGROUND: SETD2 protects against genomic instability via maintenance of homologous recombination repair (HRR) and mismatch repair (MMR) in neoplastic cells. However, it remains unclear whether SETD2 dysfunction is a complementary or independent factor to microsatellite instability-high (MSI-H) and tumor mutational burden-high (TMB-H) for immunocheckpoint inhibitor (ICI) treatment, and little is known regarding whether this type of dysfunction acts differently in various types of cancer. METHODS: This cohort study used multidimensional genomic data of 6726 sequencing samples from our cooperative and non-public GenePlus institute from April 1 through April 10, 2020. MSIsensor score, HRD score, RNAseq, mutational data, and corresponding clinical data were obtained from the TCGA and MSKCC cohort for seven solid tumor types. RESULTS: A total of 1021 genes underwent target panel sequencing reveal that SETD2 mutations were associated with a higher TMB. SETD2 deleterious mutation dysfunction affected ICI treatment prognosis independently of TMB-H (p < 0.01) and had a lower death hazard than TMB-H in pancancer patients (0.511 vs 0.757). Significantly higher MSI and lower homologous recombination deficiency were observed in the SETD2 deleterious mutation group. Improved survival rate was found in the MSKCC-IO cohort (P < 0.0001) and was further confirmed in our Chinese cohort. CONCLUSION: We found that SETD2 dysfunction affects ICI treatment prognosis independently of TMB-H and has a lower death hazard than TMB-H in pancancer patients. Therefore, SETD2 has the potential to serve as a candidate biomarker for ICI treatment. Additionally, SETD2 should be considered when dMMR is detected by immunohistochemistry.
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Reparación del ADN , Inestabilidad de Microsatélites , Neoplasias Pancreáticas , Humanos , Pueblo Asiatico , Estudios de Cohortes , Reparación de la Incompatibilidad de ADN/genética , Reparación del ADN/genética , Inestabilidad Genómica , Inmunoterapia , Mutación , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidad , Reparación del ADN por Recombinación/genéticaRESUMEN
BACKGROUND: The aims of the study were to evaluate potential differences among first-line treatment for EGFR mutant (m+) non-small cell lung cancer (NSCLC) patients with brain metastasis in China and to identify the factors influencing survival outcomes. METHODS: In this retrospective study, 172 EGFRm + patients with advanced NSCLC who received a 1st generation EGFR tyrosine kinase inhibitor (TKI) were divided into 4 groups: A, EGFR-TKI (n = 84); B, EGFR-TKI + pemetrexed + cisplatin/carboplatin chemotherapy (CT) (n = 55); C, EGFR-TKI + bevacizumab (n = 15); and D, EGFR-TKI + pemetrexed + cisplatin/carboplatin CT + bevacizumab (n = 18). Intracranial and extracranial progression-free survival (PFS), the overall survival (OS), objective remission rates (ORRs) and adverse events were analyzed. RESULTS: Intracranial PFS of groups C + D was longer than for groups A + B (18.9 m vs. 11.0 m, P = 0.027). Extracranial PFS were longer in group B in comparison with group A (13.0 m vs. 11.5 m, P = 0.039) and in groups C + D compared to groups A + B (18.9 m vs. 11.9 m, P = 0.008). Median OS in groups A and B were 27.9 m and 24.4 m, respectively, while groups C and D have not yet achieved median OS. Significant difference was found in intracranial ORR between groups A + B vs. C + D (31.0% vs. 65.2%, P = 0.002). Most patients suffered grade 1-2 treatment-related adverse events, which were relieved soon after symptomatic treatment. CONCLUSIONS: First-generation EGFR-TKI + bevacizumab treatment outperformed other regimens in EGFRm + NSCLC patients with brain metastasis. The therapy improved the control and delayed progression of intracranial lesions and prolonged survival times.
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Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Estudios Retrospectivos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Bevacizumab/uso terapéutico , Pemetrexed/uso terapéutico , Cisplatino/uso terapéutico , Carboplatino/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Resultado del Tratamiento , Pronóstico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundario , Receptores ErbB , MutaciónRESUMEN
BACKGROUND: Epidermal growth factor receptor (EGFR) mutations are often associated with non-EGFR genetic alterations, which may be a reason for the poor efficacy of EGFR tyrosine kinase inhibitors (TKIs). Here we conducted this study to explore whether EGFR-TKIs combined with chemotherapy would benefit advanced lung adenocarcinoma patients with both sensitive EGFR mutation and concomitant non-EGFR genetic alterations. METHODS: Cases of advanced lung adenocarcinoma with EGFR mutation combined with concomitant non-EGFR genetic alterations were retrospectively collected. And the patients were required to receive first-line EGFR-TKIs and chemotherapy combination or EGFR-TKIs monotherapy. Demographic, clinical and pathological data were collected, and the electronic imaging data were retrieved to evaluate the efficacy and time of disease progression. Survival data were obtained through face-to-face or telephone follow-up. The differences between the two groups in objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were investigated. RESULTS: 107 patients were included, including 63 cases in the combination group and 44 cases in the monotherapy group. The ORR were 78% and 50% (P=0.003), and DCR were 97% and 77% (P=0.002), respectively. At a median follow-up of 13.7 mon, a PFS event occurred in 38.1% and 81.8% of patients in the two groups, with median PFS of 18.8 mon and 5.3 mon, respectively (P<0.000,1). Median OS was unreached in the combination group, and 27.8 mon in the monotherapy group (P=0.31). According to the Cox multivariate regression analysis, combination therapy was an independent prognostic factor of PFS CONCLUSIONS: In patients with EGFR-mutant advanced lung adenocarcinoma with concomitant non-EGFR genetic alterations, combination of TKIs and chemotherapy was significantly superior to EGFR-TKIs monotherapy, which should be the preferred treatment option.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Receptores ErbB/genética , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico , Estudios RetrospectivosRESUMEN
In this work, a mild chemical precipitation method and simple hydrothermal treatment of the nickel hexamyanocobaltate precursor strategy are developed to prepare a sea urchin-like CoNi2S4compound with remarkable specific capacity and excellent cycling stability. The prepared CoNi2S4has an outstanding specific capacity of 149.1 mA h g-1at 1 A g-1and an initial capacity of 83.1% after 3000 cycles at 10 A g-1. Moreover, the porous carbon nanospheres (PCNs) with exhibit cycling stability (94.7% of initial specific capacity after 10 000 cycles at 10 A g-1) are selected as negative electrode to match CoNi2S4positive electrode for assembly of CoNi2S4//PCNs asymmetric supercapacitor (ASC). Satisfactorily, the as-assembled CoNi2S4//PCNs ASC exhibits an impressive energy density of 41.6 Wh kg-1at 797 W kg-1, as well as the suitable capacity retention of 82.8% after 10 000 cycles. The superior properties of the device demonstrated that the as-prepared material is potential energy storage material.
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A novel gelator molecular based on quinolone (MN) has been successfully designed and synthesized. The gelator MN could self-assemble to form a supramolecular gel (OMN), which showed obvious aggregation-induced emission (AIE) in iso-Propyl alcohol (i-PrOH). Furthermore, the supramolecular organogel OMN realized ultrasensitive detection of Fe3+ and Cu2+ in aqueous medium and fluorescent quenching at 427â¯nm. The sensing mechanism between supramolecular gel and metal ions was fully investigated via FE-SEM, FT-IR, XRD and XPS. Meanwhile, a thin film based on responsive supramolecular gel OMN was prepared, which could be used as multi-stimuli-responsive fluorescent display materials for the detection of Fe3+ and Cu2+.
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Quinolinas , Iones , Espectrometría de Fluorescencia , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
BACKGROUND: This study aimed to estimate peripheral blood lymphocyte subsets and programmed death receptor-1 positive (PD-1+) proportions of T cells, and their impact on progression free survival (PFS) and radiological response in lung cancer. METHODS: From May 2018 to April 2020, 34patients of the Henan Tumor Hospital who were diagnosed with advanced lung cancer were recruited to this study. Peripheral blood lymphocyte subsets and PD-1+ proportions of T cells were assessed by flow cytometry before and after treatment with immune checkpoint inhibitors (ICIs). The associations among these parameters, and PFS and clinical response were estimated by survival analysis and Fishers' exact test, respectively. RESULTS: Several lymphocyte variables and biomarkers were found to be correlated with PFS and tumor response, as assessed using the Response Evaluation Criteria in Solid Tumors (RECIST). In all 34 lung cancer participants and a subgroup of 28 participants with non-small cell lung cancer (NSCLC), higher levels of natural killer (NK) cells and higher CD4+/CD8+ cell ratios before the ICIs treatment were associated with longer PFS. Moreover, CD4+ T cells were significantly correlated with radiological response in all 34 lung cancer participants. Of the 28 NSCLC participants, those with higher levels of CD4+ T cells, CD4+/CD8+ cell ratios, absolute numbers of NK cells, and lower levels of regulatory T cells (Tregs)before treatment had better tumor response. After 2 cycles of combined ICIs treatment, both the absolute numbers of CD4+ T cells and CD45+ lymphocytes were statistically associated with PFS after being adjusted for gender and neutrophil-lymphocyte ratio (NLR) [hazard ratio (HR) =0.23, P=0.015; HR=0.30, P=0.032, respectively]. The absolute numbers of CD45+, CD3+, and CD4+ T lymphocytes were associated with radiological response treated by ICIs (P=0.038). CONCLUSIONS: Our results suggested that the absolute number of NK cells and CD4+/CD8+ cells ratio before treatment could predict longer PFS and better radiological response in lung cancer patients treated with ICIs combination therapy. In addition, Tregs, as well as the other parameters in lymphocyte subsets, may also predict response.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Humanos , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares/tratamiento farmacológico , Subgrupos Linfocitarios , Análisis de SupervivenciaRESUMEN
OBJECTIVE: This study aimed to determine whether there is a difference in the efficacy of nivolumab in patients with advanced non-small cell lung cancer (NSCLC) presenting with or without brain metastases. MATERIALS AND METHODS: Patients with advanced NSCLC treated with nivolumab monotherapy were retrospectively analyzed. They were divided into two cohorts according to the presence or absence of brain metastases. The differences between the two cohorts in objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), duration of response (DOR) and overall survival (OS) were investigated, and the intracranial efficacy, including intracerebral objective response rate (IORR), intracranial disease control rate (IDCR) and intracranial progression-free survival (iPFS), were examined in the brain metastasis (BM) cohort. RESULTS: Seventy-three patients (32 with brain metastases and 41 without) were included. The ORRs of the BM cohort and the non-brain metastasis (non-BM) cohort were 25.0% and 19.5% (p = 0.574), DCRs were 53.1% and 56.1% (p = 0.800), respectively. Their median PFS were 2.8 and 4.9 months (p = 0.204), median DORs were 9.8 and 28.8 months (p = 0.003), and median OS were 14.8 and 20.2 months (p = 0.114), respectively. According to the Cox multivariate regression analysis, BM was not an independent prognostic factor. The IORR and IDCR of the BM cohort were 28.1% and 46.9%, respectively, with a median iPFS of 2.2 months. CONCLUSIONS: The efficacy of nivolumab is comparable in patients with NSCLC presenting with and without brain metastases, but the results must be verified in large-scale prospective studies.
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Antineoplásicos Inmunológicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Nivolumab/uso terapéutico , Antineoplásicos Inmunológicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/patología , Estudios de Cohortes , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Nivolumab/farmacología , Estudios RetrospectivosRESUMEN
Retrospective analysis of data from 14,528 lung cancer patients with multiple primary malignant neoplasm (MPMN) revealed that 2.5% (364/14,528) were MPMN cases and 96.2% (350/364) were diagnosed with two primary malignancies, 3.6% (13/364) with three primary malignancies, and 0.3% (1/364) with four primary malignancies. Among 350 lung cancer patients diagnosed with two primary malignancies, 26.6% (93/350) had lung cancer diagnosed first (LCF) and 73.4% (257/350) had other cancers diagnosed initially (OCF), whereas synchronous MPMN (SMPMN) accounted for 21.1% (74/350) and metachronous MPMN (MMPMN) accounted for 78.9% (276/350) of the cases. Detection of first primary neoplasms were at an early stage for LCF patients and the age of the first lung cancer diagnosis was 59.3 years vs. 55.4 years in the OCF group (P = 0.008), whereas the onset age of second primary neoplasm diagnosis was similar in both groups (62.5 and 61.6 years, P = 0.544). Median survival times of MMPMN and SMPMN patients in the LCF group were 6.83 and 2.42 years and in the OCF group 8.67 years and 2.25 years, respectively. Multivariate analysis showed that SMPMN, LCF and the age of the primary cancer diagnosed first ( ≥ 60 years) and NSCL staging > II were significant independent factors for inferior prognosis of patients.
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Neoplasias Pulmonares/epidemiología , Neoplasias Primarias Múltiples/epidemiología , Edad de Inicio , Anciano , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Neoplasias Primarias Múltiples/diagnóstico , Neoplasias Primarias Múltiples/etiología , Neoplasias Primarias Múltiples/mortalidad , Pronóstico , Modelos de Riesgos Proporcionales , Vigilancia en Salud PúblicaRESUMEN
OBJECTIVE: De novo mesenchymal-epithelial transition (MET) amplification is believed to promote primary resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in the non-squamous non-small cell lung cancer (NSCLC). We sought to seek the treatment of a patient with EGFR-mutant NSCLC harboring de novo MET amplification. MATERIALS AND METHODS: After clinical diagnosis, tissue and plasma samples were obtained from the patient and subjected to next-generation sequencing to identify and dynamic monitor the mutations. RESULTS: The patient was treated with gefitinib monotherapy in the beginning and experienced primary resistance to gefitinib but achieved a good response to the combination therapy of gefitinib and crizotinib. He achieved a 16.8-month progress free survival with the combination therapy. NGS of plasma circulating cell-free tumor DNA shown that L858R mutation was no longer detectable and the copy number of MET dropped when the patient got remission. CONCLUSIONS: The combination of EGFR- and MET- tyrosine kinase inhibitors may be an effective treatment for the rare mutations.
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Carcinoma de Pulmón de Células no Pequeñas/terapia , Crizotinib/uso terapéutico , Gefitinib/uso terapéutico , Línea Celular Tumoral , Transición Epitelial-Mesenquimal , Receptores ErbB , Humanos , Neoplasias Pulmonares , Masculino , Persona de Mediana Edad , Mutación , Inhibidores de Proteínas QuinasasRESUMEN
OBJECTIVE: The objective of this study was to investigate whether first-line treatment with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in combination with chemotherapy improves the prognosis of patients with advanced non-small cell lung cancer (NSCLC) who harbour low-abundance EGFR mutations. PATIENTS AND METHODS: We retrospectively analysed the clinical data of 76 patients with advanced NSCLC who harboured low-abundance EGFR mutations. The patients were divided into the combination group and the monotherapy group. The combination group received EGFR-TKI combined with a platinum-based regimen. After the end of chemotherapy, EGFR-TKI was administered daily. The monotherapy group was administered EGFR-TKI therapy daily. RESULTS: No significant difference was observed in response rate between the different groups. The median PFS and OS were significantly longer in the combination group than in the monotherapy group (PFS: 7.9 months [95% CI,5.73-10.07] vs 5.9 months [95% CI, 4.99-6.81], p = 0.015; OS: 25.8 months[95% CI,16.27-35.33] vs 19.8 months [95% CI, 18.60-21.00], p = 0.047). Subgroup analysis showed that, for patients with the exon 21 L858R mutation, the PFS and OS were significantly longer in the combination group than in the monotherapy group (PFS: 7.2 months vs 5.8 months, p = 0.013; OS: 22.0 months vs 18.7 months, p = 0.024). The incidence of adverse events was significantly higher in the combination group. CONCLUSION: For patients with advanced NSCLC and low-abundance EGFR mutations, first-line treatment with EGFR-TKI plus chemotherapy significantly improved PFS and OS. The combination therapy increased the incidence of adverse reactions, but all adverse reactions were expected and tolerated.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mutación , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/genética , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Tasa de Mutación , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Inhibidores de Proteínas Quinasas/administración & dosificación , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
PURPOSE: To evaluate the efficacy of maintenance apatinib after chemotherapy for extensive-stage (ED) small-cell lung cancer (SCLC). PATIENTS AND METHODS: This was a retrospective analysis of 23 cases of extensive-stage SCLC admitted to the Affiliated Cancer Hospital of Zhengzhou University from January 2015 to December 2017. The patients without progression after induction chemotherapy received apatinib 250 mg per day until disease progression or unacceptable toxicity occurred. We analyzed the median progression-free survival (PFS), median overall survival (OS) and safety. RESULTS: Of 23 enrolled patients, 1 was lost to follow-up. The median PFS from the time of maintenance therapy was 4.1 months (95% CI 3.63-4.57 months). The median PFS from the time of induction chemotherapy was 8.3 months (95% CI 7.20-9.40 months). The median OS from the time of maintenance therapy was 12.5 months (95% CI 5.51-19.49 months). The median OS from the time of induction chemotherapy was 17.0 months (95% CI 9.86-24.14 months). The most frequent treatment-related adverse events were hand-foot syndrome (43.5%, 10/23) and secondary hypertension (30.4%, 7/23), followed by fatigue, proteinuria, nausea, and oral mucositis (17.4%, 13.0%, 13.0%, and 8.7%, respectively). Hematologic toxicity included thrombocytopenia (30.4%), leucopenia (26.1%), and anemia (17.4%). The main grade 3 or 4 toxicities were hand-foot syndrome (8.7%, 2/23) and hypertension (4.3%, 1/23). CONCLUSION: Maintenance apatinib was safe and achieved encouraging PFS and OS in extensive-stage SCLC.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Quimioterapia de Mantención , Piridinas/efectos adversos , Piridinas/uso terapéutico , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Anciano , Neoplasias Encefálicas/secundario , Femenino , Humanos , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Piridinas/administración & dosificación , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
BACKGROUND: Bevacizumab combined with platinum-based chemotherapy has been recommended as the first-line agent in advanced nonsquamous non-small cell lung cancer (NSCLC) without driven gene, but this regimen is not common in the second-line or later-line treatment of non-squamous NSCLC. The aim of this study is to investigate the efficacy and safety of bevacizumab combined with chemotherapy as second-line or later-line treatment in advanced non-squamous NSCLC. METHODS: We retrospectively reviewed the clinical data of advanced nonsquamous NSCLC patients who were treated with bevacizumab after first-line treatment failure and they were hospitalized in the Affiliated Cancer Hospital of Zhengzhou University from January 2014 to June 2017, and Kaplan-Meier method, Log-rank test and Cox model were used for analysis. RESULTS: A total of 62 patients were included in the analysis. The total objective response rate (ORR) was 32.2%, and the disease control rate (DCR) was 96.8%. The median progression-free survival (PFS) was 6.4 months (95%CI: 6.05-6.83), and the median overall survival (OS) was 20.4 months (95%CI: 12.98-27.76). In the subgroup analysis, there was no significant difference in median PFS between patients with brain metastases and those without brain metastases (6.2 months vs 6.4 months, P=0.052). Cycles of bevacizumab (>6 or ≤6 cycles) was an independent influencing factor of PFS (P=0.004). The most common adverse events were leukopenia, fatigue, nausea, thrombocytopenia and hypertension. CONCLUSIONS: In the second-line or later-line treatment, bevacizumab combined with chemotherapy is an effective and safe regimen for advanced non-squamous NSCLC.
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Bevacizumab/efectos adversos , Bevacizumab/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Seguridad , Anciano , Neoplasias Encefálicas/secundario , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: To investigate the influence of mutation abundance and sites of epidermal growth factor receptor (EGFR) on therapeutic efficacies of EGFR-tyrosine kinase inhibitor (EGFR-TKIs) treatments of patients with advanced non-small cell lung carcinoma (NSCLC). METHODS: EGFR mutational sites and mutation abundance were analyzed by amplification refractory mutation system (ARMS) in paraffin-embedded tissue sections taken from primary or metastatic tumors of 194 NSCLC patients. RESULTS: The median progression-free survival (PFS) time of the enrolled patients was 9.3 months (95% CI, 8.2-10.8 months). The PFS was significantly different with EGFR gene mutation abundance after EGFR-TKI therapy (P = 0.014). The median PFS was significantly longer when the cut-off value of EGFR mutation abundance of exon 19 or exon 21, and solely exon 19 was > 26.7% and 61.8%, respectively. For patients who received EGFR-TKI as first-line treatment, the median PFS was significantly longer in the high mutation abundance group than in the low mutation abundance group (12.7 vs 8.7 months, P = 0.002). CONCLUSION: The PFS benefits were greater in patients with a higher abundance of exon 19 deletion mutations in the EGFR gene after EGFR-TKI treatment and first line EGFR-TKI treatment led to improved PFS in high mutation abundance patients.
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Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/genética , Antineoplásicos/uso terapéutico , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico , Adenocarcinoma del Pulmón/patología , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/farmacología , Receptores ErbB/genética , Exones , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Inhibidores de Proteínas Quinasas/farmacología , Curva ROC , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: The goal of this study was to assess the survival of patients with acquired resistance to gefitinib who underwent different subsequent treatments. METHODS: From September 2007 to July 2014, a total of 103 patients with pathologically confirmed advanced non-small cell lung cancer and acquired resistance to gefitinib were retrospectively analyzed. Fifty-eight (56%) patients received chemotherapy; 36 were treated with chemotherapy and gefitinib continuation (CT + G), and 22 patients received chemotherapy (CT) alone. Twenty-two patients (22%) received continued gefitinib medication and local therapy (LT + G), and 23 (22%) received best supportive care (BSC). FINDINGS: The median age of the patients was 62 years and 99 (96%) were diagnosed with adeno-carcinoma and 93 (90%) were stage IV cases. In the chemotherapy groups, patients had high objective response rates and disease control rates (CT + G, 16.7% and 42.7%; CT, 9.1% and 40.9%, respectively). The median progression-free survival times from the beginning of gefitinib resistance was 5.3 months in the CT + G group, 3.6 months in the CT group, 3.1 months in the LT + G group, and 1.4 months in the BSC group (P < 0.005). Moreover, the median overall survival time after gefitinib resistance in the CT + G group was 11.6 months, which was significantly longer than for CT (9.6 months), LT + G (8.1 months), and BSC (3.7 months) patients (P < 0.001). IMPLICATIONS: Subsequent chemotherapy after acquired gefitinib resistance led to better survival rates, particularly when combined with continued gefitinib treatment. Local treatment combined with continued gefitinib is an alternative therapy when local progression has occurred. However, larger sample size studies in similar or other population groups are necessary to validate these findings.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Quinazolinas/administración & dosificación , Adulto , Anciano , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Gefitinib , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To compare the efficacy of gefitinib monotherapy across different age groups of patients with advanced lung adenocarcinoma. METHODS: Clinical data of patients (mostly Chinese) with advanced lung adenocarcinoma who were non-smokers or light smokers and had received oral gefitinib (250mg/d) between October 2006 and December 2009 were reviewed retrospectively. The 93 enrolled patients (25 male and 68 female; median age, 62.5 years), were divided into three age groups: < or = 49 years (n = 22), 50-69 years (n = 53), and > or = 70 years (n = 18). Among them, 84 patients had received at least one chemotherapy regimen previously. The objective response rate (ORR), time to disease progression (TTP), median overall survival (MOS) and adverse effects in response to gefitinib treatment were analyzed in the above age groups. RESULTS: Out of 93 patients, a complete response was seen in 5 patients, partial response in 43 patients, stable disease in 36 patients, and disease progression in 9 patients. ORR was 51.6%, and the disease control rate (DCR) was 90.3%. No significant correlation was observed between ORR of gefitinib treatment and the baseline clinical characteristics of the patients. The median TTP was 12.6 months, and median overall survival (MOS) was 23.4 months. Gefitinib treatment-related UP was prolonged with increasing age: 8.2 months, 14.2 months and 18.2 months in the age groups of < or = 49-years, 50-69-years and > or = 70-years, respectively (log-rank P = 0.002). MOS in the three age groups was 20.4 months, 23.6 months and 22.0 months, respectively (P > 0.05). The most common adverse effects were rash and diarrhoea, and rash seemed to be correlated with ORR (ORR = 2.631; p = 0.044, 95% CI: 1.025-6.753). CONCLUSIONS: In Asian patients with advanced lung adenocarcinoma who were non-smokers or light smokers and were treated with gefitinib, progression-free survival was correlated with age. Elderly patients (> or = 70 years) seemed more likely to benefit from gefitinib treatment.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Envejecimiento/fisiología , Antineoplásicos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Quinazolinas/uso terapéutico , Adenocarcinoma/patología , Adulto , Anciano , Antineoplásicos/efectos adversos , Progresión de la Enfermedad , Femenino , Gefitinib , Humanos , Estimación de Kaplan-Meier , Modelos Logísticos , Neoplasias Pulmonares/patología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Quinazolinas/efectos adversos , Estudios Retrospectivos , Programas Informáticos , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
Postoperative recurrence is the main cause of primary treatment failure in the resectable non-small cell lung cancer (NSCLC). Systematic treatments should be taken to decrease the recurrence. Adjuvant chemotherapy, including neoadjuvant chemotherapy, postoperative adjuvant chemotherapy and targeted therapy, is a widely used in this area. In this review, we summarize the clinical trials and meta-analysis related to the adjuvant chemotherapy and targeted therapy in patients with early stage NSCLC.