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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. e13586-e13586
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 26, No. 23 ( 2020-12-01), p. 6168-6175
    Abstract: Dynamic biomarker monitoring may inform pathways for treating EGFR-T790M–positive non–small cell lung cancer (NSCLC) and central nervous system (CNS) metastases with osimertinib. This study aimed to determine the efficacy and safety of osimertinib for real-world patients with EGFR-T790M NSCLC and CNS metastases and to explore potential circulating biomarkers of therapeutic response. Patients and Methods: APOLLO (ClinicalTrials.gov registration: NCT02972333) was a prospective, single-arm, open-label trial which ran from January 2017 to April 2019. Eligible patients had confirmed EGFR-T790M–positive NSCLC, prior treatment with an EGFR-tyrosine kinase inhibitor, and CNS metastases. All enrolled patients received oral osimertinib 80 mg once daily until disease progression or intolerable toxicity. Primary outcome was overall progression-free survival (PFSo) and secondary outcomes included objective response rate (ORR) and adverse events (AE). Exploratory biomarker analysis involved collection of plasma and cerebrospinal fluid (CSF) samples for next-generation sequencing and drug penetration analysis. Results: From January to September 2017, 38 patients were enrolled. After a median follow-up of 8.2 months (range, 0.07–15.6), 23 (60.5%) of 38 patients had disease progression or death. Median PFSo was 8.4 months [95% confidence interval (CI), 5.8–10.9]. Overall ORR was 39.4%. Twelve (31.6%) of 38 patients had ≥1 grade 3–4 AE. Median osimertinib CSF penetration rate was 31.7%. Patients with undetectable plasma EGFR mutations at week 6 had improved PFSo compared with those with detectable mutations (not reached vs. 4.5 months; 95% CI, 0.0–1.1; P & lt; 0.05). Conclusions: Osimertinib had potent activity against EGFR-T790M–positive NSCLC with CNS metastases. Dynamic monitoring of plasma EGFR may suffice for predicting clinical responses, mitigating the need for repeat CSF biopsy. See related commentary by Marmarelis and Bauml, p. 6077
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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  • 3
    In: Evidence-Based Complementary and Alternative Medicine, Hindawi Limited, Vol. 2021 ( 2021-12-13), p. 1-15
    Abstract: Objective. This study aimed to compare the efficacy of different first-line strategies based on different EGFR mutation types (19 deletion and 21 Leu858Arg mutations). Methods. We conducted a systematic review and network meta-analysis (NMA) by searching and analyzing RCTs on PubMed, Embase, Cochrane Library, ASCO.org, and ESMO.org, from inception to September 30th, 2020. Results. Nineteen RCTs involving 5450 patients were finally included in this study, covering 10 different treatment strategies. The Bayesian ranking results suggested that, in terms of PFS, in the overall population and in patients with 19del mutation, osimertinib was most likely to rank the first, with the cumulative probabilities of 41.89% and 45.73%, respectively, while for patients with 21 Leu858Arg mutation, standard of care (SoC, represents first-generation EGFR-TKIs in this NMA) + chemotherapy was most likely to rank the first, with the cumulative probabilities of 30.81% in PFS. Moreover, SoC + chemotherapy provided the best overall survival benefit for the overall population and patients with 19del, with the cumulative probabilities of 57.85% and 33.51%, respectively. In contrast, for patients with 21 Leu858Arg mutation, dacomitinib showed the most favorable overall survival, with the cumulative probabilities of 36.73%. Conclusions. In this NMA, osimertinib and SoC combined with chemotherapy would be the optimal first-line treatment options for advanced NSCLC patients harboring EGFR 19 deletion mutation and 21 Leu858Arg mutation, respectively. This finding is likely to be adopted in clinical practice and provide guidance for future clinical study design. Systematic review registration: INPLASY2020100059.
    Type of Medium: Online Resource
    ISSN: 1741-4288 , 1741-427X
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2021
    detail.hit.zdb_id: 2148302-4
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  • 4
    In: BMC Immunology, Springer Science and Business Media LLC, Vol. 19, No. 1 ( 2018-12)
    Type of Medium: Online Resource
    ISSN: 1471-2172
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2018
    detail.hit.zdb_id: 2041500-X
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  • 5
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2023
    In:  Cell Communication and Signaling Vol. 21, No. 1 ( 2023-03-03)
    In: Cell Communication and Signaling, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2023-03-03)
    Abstract: Dysregulated ARID1A expression is frequently detected in lung adenocarcinoma (LUAD) and mediates significant changes in cancer behaviors and a poor prognosis. ARID1A deficiency in LUAD enhances proliferation and metastasis, which could be induced by activation of the Akt signaling pathway. However, no further exploration of the mechanisms has been performed. Methods Lentivirus was used for the establishment of the ARID1A knockdown (ARID1A-KD) cell line. MTS and migration/invasion assays were used to examine changes in cell behaviors. RNA-seq and proteomics methods were applied. ARID1A expression in tissue samples was determined by IHC. R software was used to construct a nomogram. Results ARID1A KD significantly promoted the cell cycle and accelerated cell division. In addition, ARID1A KD increased the phosphorylation level of a series of oncogenic proteins, such as EGFR, ErbB2 and RAF1, activated the corresponding pathways and resulted in disease progression. In addition, the bypass activation of the ErbB pathway, the activation of the VEGF pathway and the expression level changes in epithelial–mesenchymal transformation biomarkers induced by ARID1A KD contributed to the insensitivity to EGFR-TKIs. The relationship between ARID1A and the sensitivity to EGFR-TKIs was also determined using tissue samples from LUAD patients. Conclusion Loss of ARID1A expression influences the cell cycle, accelerates cell division, and promotes metastasis. EGFR -mutant LUAD patients with low ARID1A expression had poor overall survival. In addition, low ARID1A expression was associated with a poor prognosis in EGFR -mutant LUAD patients who received first-generation EGFR-TKI treatment.
    Type of Medium: Online Resource
    ISSN: 1478-811X
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2126315-2
    SSG: 12
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  • 6
    In: Thoracic Cancer, Wiley, Vol. 13, No. 1 ( 2022-01), p. 107-116
    Abstract: There is limited data on the clinical outcome, long‐term survival and tolerability of sequential therapy of first‐line crizotinib followed by alectinib in a real‐world setting for Chinese patients with advanced ALK+ NSCLC. Methods The medical records of patients who received sequential therapy with first‐line crizotinib followed by alectinib (no intermittent systemic therapy was allowed between the two ALK‐TKIs) were collected from six centers in China. Combined time treatment to failure (C‐TTF) was defined as the period from the start of crizotinib to the complete discontinuation of alectinib due to any cause. Results A total of 61 patients were included in our study. Fifty‐two patients were switched to alectinib due to disease progression, seven as a result of toxicity, and two due to patient preference. At the time of data cutoff, alectinib treatment was discontinued in 31 patients on account of disease progression while severe adverse events resulted in cessation of alectinib in another two patients. Rebiopsy was conducted in 21 patients following disease progression on alectinib in whom ALK secondary mutation was found in 13 patients. Patients with ALK secondary mutation demonstrated better PFS during treatment with subsequent ALK‐TKIs compared with those without (10.4 vs. 3.1 m, p  = 0.0018, HR = 0.08). With a median follow‐up of 34.3 months, C‐TTF was 39.2 months and estimated 5‐year OS was 68.6% in the overall population. Conclusion Sequential therapy with first‐line crizotinib followed by alectinib demonstrated long‐term benefits. Different efficacy in subsequent ALK‐TKI between patients with or without ALK secondary mutation further emphasized the importance of rebiopsy to guide targeted therapy more precisely.
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2559245-2
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  • 7
    In: Thoracic Cancer, Wiley, Vol. 12, No. 24 ( 2021-12), p. 3407-3415
    Abstract: Dacomitinib is a second‐generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) which is superior to first‐generation EGFR TKI in ARCHER 1050. However, the activity of dacomitinib in the central nervous system (CNS) is not known as ARCHER 1050 did not include patients with baseline brain metastases. This study aimed to describe dacomitinib's activity in the CNS in a real‐world setting. Patients and Methods Thirty‐two patients who were receiving dacomitinib for advanced non‐small‐cell lung cancer (NSCLC) with EGFR mutations and brain metastasis were included in this study. Patients who received prior EGFR TKIs were excluded from this trial. Case report forms were collected to determine treatment outcomes. Results Among 32 patients with EGFR‐mutated NSCLC and brain disease, eight were included in the CNS evaluable for response group. The intracranial objective response rate (iORR) was 87.5% (95% confidence interval [CI] 47.3–99.7%) and the intracranial disease control rate (iDCR) was 100% (95% CI 63.1–100%). In 30 evaluable patients with measurable or nonmeasurable brain lesions, the iORR was 66.7% (95% CI 47.2–82.7%) and the iDCR was 100% (95% CI 88.4–100%). Median intracranial duration of response (iDoR) and intracranial progression‐free survival (iPFS) were not reached, with a one‐year iDoR rate of 72.2% (95% CI 48.7–95.7%) and a 1‐year iPFS rate of 71.2% (95% CI 51.0–91.4%), respectively. The majority of patients experienced low‐grade (G1/2) toxicities, which are reversible. Conclusion This study suggests that dacomitinib demonstrated CNS efficacy in patients with EGFR TKI‐naïve EGFR‐mutated NSCLC in the real‐world setting. The safety profile was tolerable and manageable.
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2559245-2
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  • 8
    In: Thoracic Cancer, Wiley, Vol. 13, No. 4 ( 2022-02), p. 557-562
    Abstract: There is a need for the development of therapies to delay cancer progression and prolong survival after initial chemotherapy for the treatment of small cell lung cancer (SCLC). Since apatinib has been found to exert promising effects on cancer patients after standard first‐line chemotherapy, this study aimed to investigate apatinib as a maintenance treatment following first‐line chemotherapy in extensive disease (ED)‐SCLC. Methods The primary endpoints were overall survival (OS) and progression‐free survival (PFS). The secondary endpoints included toxicity and safety. Apatinib (250 mg/day) was administered during the chemotherapy interval and as maintenance therapy after 4–6 cycles until the patient's disease progressed, the patient died, or became intolerant to the drug's toxicity. Results The patients who received apatinib maintenance treatment had a median PFS of 3.7 months (95% CI: 1.3–6.2 months). The median OS was 16.3 months (95% CI: 9.7–22.8 months). The objective response rate and disease control rate were 50.0% and 66.7%, respectively. Two patients required dose reduction due to adverse effects (AEs). The most common AEs included hypertension ( n  = 4, 33.3%) and hand‐foot‐skin reaction ( n  = 2, 16.7%). One patient developed diarrhea, while another patient developed hemoptysis. The most serious AE was intestinal obstruction. Conclusions Apatinib maintenance therapy showed promising efficacy and safety to extend the OS/PFS of patients with ED‐SCLC, thus making it a potent therapeutic option in future clinical practice. Given the small sample size of this study, further studies with large sample sizes are needed to validate the findings of the present study.
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2559245-2
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  • 9
    In: Thoracic Cancer, Wiley, Vol. 8, No. 5 ( 2017-09), p. 482-488
    Abstract: This study was conducted to evaluate the value of gemcitabine combined with cisplatin as adjuvant chemotherapy for radical resection of non‐small cell lung cancer. Methods Data of 100 patients who had undergone radical resection of non‐small cell lung cancer and were treated with cisplatin/gemcitabine as adjuvant chemotherapy between J une 2007 and D ecember 2010 at the C hinese A cademy of M edical S ciences were reviewed . Results The median age was 59 years (range 36–73); 82% of the patients were male. Forty‐two percent had adenocarcinoma and 55% had squamous cell carcinoma. Most patients had pathologic IIB (29%) and IIIA (44%) stage disease. Eighty‐five percent of patients completed four cycles of chemotherapy, with 76% completing the planned full dose. The main reason for a reduced gemcitabine dose in 13 patients was grade 3/4 neutropenia or thrombocytopenia. The median dose and dose intensity were 8377.1 mg/m 2 and 708 mg/(m 2 /week) for gemcitabine and 293.38 mg/m 2 and 25.24 mg/(m 2 /week) for cisplatin, respectively. During follow‐up the median disease‐free survival was 33.8 months (95% confidence interval [ CI ] 15.938–51.676). Patients with squamous cell carcinoma (hazard ratio [ HR] 0.404, 95% CI 0.241–0.676; P  = 0.001) and pathologic stage I ( HR 4.379, 95% CI 1.721–11.142; P  = 0.002) achieved better disease‐free survival. The survival rates at one, two, and five years were 94%, 77%, and 55%, while the survival rates without recurrence were 64%, 53%, and 39%, respectively. Conclusion As an adjuvant chemotherapy regimen, gemcitabine with cisplatin is well tolerated. Patients with squamous cell carcinomas or pathologic stage I achieve better results.
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2559245-2
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  • 10
    In: Thoracic Cancer, Wiley, Vol. 6, No. 3 ( 2015-05), p. 233-238
    Abstract: The treatment status of small cell lung cancer ( SCLC ) in Mainland C hina has never been reported; therefore, this study is the first multicenter survey investigating the status of epidemiology and treatment options of SCLC in Mainland C hina. Methods Two questionnaires were designed to obtain information in 12 medical centers in five major C hinese cities. The hospital information questionnaire was designed to outline SCLC patients' characteristics and treatment preferences in each medical institution, and the patient information questionnaire collected detailed treatment information of 298 SCLC cases in these hospitals. Results SCLC represented 13.7% and 18.3% of all lung cancer patients in 2005 and 2010, respectively. Clinical management of SCLC follows mainstream clinical guidelines in general. The most widely applied first‐line treatment mode for limited‐stage patients was combined chemoradiotherapy (66.2%), while 77.0% of the extensive‐stage patients received chemotherapy alone as initial treatment. Etoposide with cisplatin or carboplatin were the most accepted first‐line chemotherapy regimens. The objective response rate was 58.3% after first‐line chemotherapy and 23% of the patients who responded well to first‐line treatment received prophylactic cranial irradiation. As for second‐line chemotherapy, single regimen topotecan or a combined regimen containing topotecan were preferred (53.0%). Conclusions The treatment options indicated in our study are in accordance with the international clinical guidelines, which is valuable for the improvement of future guidelines, health care standard, and even the better distribution of health care resources in C hina.
    Type of Medium: Online Resource
    ISSN: 1759-7706 , 1759-7714
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2015
    detail.hit.zdb_id: 2559245-2
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