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  • 1
    Online Resource
    Online Resource
    PAPPA2 mutation as a novel indicator stratifying beneficiaries of immune checkpoint inhibitors in skin cutaneous melanoma and non‐small cell lung cancer
    Wiley ; 2022
    In:  Cell Proliferation Vol. 55, No. 9 ( 2022-09)
    Details
    In: Cell Proliferation, Wiley, Vol. 55, No. 9 ( 2022-09)
    Abstract: Pappalysin 2 ( PAPPA2 ) mutation, occurring most frequently in skin cutaneous melanoma (SKCM) and non‐small cell lung cancer (NSCLC), is found to be related to anti‐tumour immune response. However, the association between PAPPA2 and the efficacy of immune checkpoint inhibitors (ICIs) therapy remains unknown. Methods To analyse the performance of PAPPA2 mutation as an indicator stratifying beneficiaries of ICIs, seven public cohorts with whole‐exome sequencing (WES) data were divided into the NSCLC set ( n  = 165) and the SKCM set ( n  = 210). For further validation, 41 NSCLC patients receiving anti‐PD‐(L)1 treatment were enrolled in China cohort ( n  = 41). The mechanism was explored based on The Cancer Genome Atlas database ( n  = 1467). Results In the NSCLC set, patients with PAPPA2 mutation (PAPPA2‐Mut) demonstrated a significantly superior progress free survival (PFS, hazard ratio [HR], 0.28 [95% CI, 0.14–0.53] ; p   〈  0.001) and objective response rate (ORR, 77.8% vs. 23.2%; p   〈  0.001) compared to those with wide‐type PAPPA2 (PAPPA2‐WT), consistent in the SKCM set (overall survival, HR, 0.49 [95% CI: 0.31–0.78], p   〈  0.001; ORR, 34.1% vs. 16.9%, p  = 0.039) and China cohort. Similar results were observed in multivariable models. Accordingly, PAPPA2 mutation exhibited superior performance in predicting ICIs efficacy compared with other published ICIs‐related gene mutations, such as EPHA family, MUC16 , LRP1B and TTN , etc. In addition, combined utilization of PAPPA2 mutation and tumour mutational burden (TMB) could expand the identification of potential responders to ICIs therapy in both NSCLC set (HR, 0.36 [95% CI: 0.23–0.57], p   〈  0.001) and SKCM set (HR, 0.51 [95% CI: 0.34–0.76], p   〈  0.001). Moreover, PAPPA2 mutation was correlated with enhanced anti‐tumour immunity including higher activated CD4 memory T cells level, lower Treg cells level, and upregulated DNA damage repair pathways. Conclusions Our findings indicated that PAPPA2 mutation could serve as a novel indicator to stratify beneficiaries from ICIs therapy in NSCLC and SKCM, warranting further prospective studies.
    Type of Medium: Online Resource
    ISSN: 0960-7722 , 1365-2184
    URL: Issue
    URL: Article
    DOI: 10.1111/cpr.v55.9
    DOI: 10.1111/cpr.13283
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2019986-7
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Dynamics of peripheral T cell clones during PD-1 blockade in non-small cell lung cancer
    Springer Science and Business Media LLC ; 2020
    In:  Cancer Immunology, Immunotherapy Vol. 69, No. 12 ( 2020-12), p. 2599-2611
    Details
    In: Cancer Immunology, Immunotherapy, Springer Science and Business Media LLC, Vol. 69, No. 12 ( 2020-12), p. 2599-2611
    Type of Medium: Online Resource
    ISSN: 0340-7004 , 1432-0851
    URL: Article
    DOI: 10.1007/s00262-020-02642-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 1458489-X
    detail.hit.zdb_id: 195342-4
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  • 3
    Online Resource
    Online Resource
    AENEAS: A Randomized Phase III Trial of Aumolertinib Versus Gefitinib as First-Line Therapy for Locally Advanced or MetastaticNon–Small-Cell Lung Cancer With EGFR Exon 19 Deletion or L858R Mutations
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 27 ( 2022-09-20), p. 3162-3171
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 27 ( 2022-09-20), p. 3162-3171
    Abstract: Aumolertinib (formerly almonertinib; HS-10296) is a novel third-generation epidermal growth factor receptor tyrosine kinase inhibitor approved in China. This double-blind phase III trial evaluated the efficacy and safety of aumolertinib compared with gefitinib as a first-line treatment for locally advanced or metastatic EGFR-mutated non–small-cell lung cancer (NSCLC; ClinicalTrials.gov identifier: NCT03849768 ). METHODS Patients at 53 sites in China were randomly assigned 1:1 to receive either aumolertinib (110 mg) or gefitinib (250 mg) once daily. The primary end point was progression-free survival (PFS) per investigator assessment. RESULTS A total of 429 patients who were naïve to treatment for locally advanced or metastatic NSCLC were enrolled. PFS was significantly longer with aumolertinib compared with gefitinib (hazard ratio, 0.46; 95% CI, 0.36 to 0.60; P 〈 .0001). The median PFS with aumolertinib was 19.3 months (95% CI, 17.8 to 20.8) versus 9.9 months with gefitinib (95% CI, 8.3 to 12.6). Objective response rate and disease control rate were similar in the aumolertinib and gefitinib groups (objective response rate, 73.8% and 72.1%, respectively; disease control rate, 93.0% and 96.7%, respectively). The median duration of response was 18.1 months (95% CI, 15.2 to not applicable) with aumolertinib versus 8.3 months (95% CI, 6.9 to 11.1) with gefitinib. Adverse events of grade ≥ 3 severity (any cause) were observed in 36.4% and 35.8% of patients in the aumolertinib and gefitinib groups, respectively. Rash and diarrhea (any grade) were observed in 23.4% and 16.4% of patients who received aumolertinib compared with 41.4% and 35.8% of those who received gefitinib, respectively. CONCLUSION Aumolertinib is a well-tolerated third-generation epidermal growth factor receptor tyrosine kinase inhibitor that could serve as a treatment option for EGFR-mutant NSCLC in the first-line setting.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.21.02641
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 4
    Online Resource
    Online Resource
    Programmed cell death-1 (PD-L1) expression and Fibroblast growth factor receptor 1 (FGFR1) amplification in Chinese stage III/IV lung squamous lung carcinoma (SQC).
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 15_suppl ( 2015-05-20), p. e19127-e19127
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 15_suppl ( 2015-05-20), p. e19127-e19127
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2015.33.15_suppl.e19127
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
    detail.hit.zdb_id: 2005181-5
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  • 5
    Online Resource
    Online Resource
    Prognostic prediction of pemetrexed-platinum chemotherapeutic regimen for NSCLC by serum metabolomics.
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. e20603-e20603
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. e20603-e20603
    Abstract: e20603 Background: Pemetrexed-platinum chemotherapeutic doublet has become a standard schedule as the first-line treatment for advanced non-squamous NSCLC due to its promising efficacy and a favorable toxicity profile. However, chemotherapy resistance inevitably limits the therapeutic effect of this preferred chemotherapeutic regimen, especially for these intrinsically resistant patients. Development of predictive biomarkers to identify those patients who can benefit from this pemetrexed-based regimen has great significance for personalized chemotherapy. Methods: Total 354 patients who were diagnosed with inoperable stage IIIB or IV lung adenocarcinoma (LADC), assigned to receive pemetrexed-platinum doublet chemotherapy as the first-line treatment were enrolled into this prospective study, including 251 cases diagnosed ahead as training set for predictive model establishment and the subsequently diagnosed 103 cases into validation set. Ultraperformance liquid chromatography coupled to mass spectrometry (UPLC-MS) analytical platform were applied to perform the metabolic profiling studies of pre-treatment serum samples. Results: In the training set, eight potential biomarkers, comprising of hypotaurine, taurine, choline, betaine, dimethylglycine, uridine, dodecanoylcarnitine and L-palmitoylcarnitine, were discovered to be differentially expressed between the patients in disease progressive group (PD, n = 53) and disease control group (including CR, PR and SD, n = 198). In the validation set (PD vs non-PD: 23 vs 80), targeted quantitative analysis of these metabolic biomarkers revealed similar levels as that observed in the training set. Logistic regression model was accordingly established based on this eight-metabolic biomarker panel, to discriminate patients who might benefit from this chemotherapy regimen with over 90% accuracy. Conclusions: This prospective study identified blood-based biomarker panel by metabonomics analysis could predict the clinical outcome of pemetrexed-platinum chemotherapy prior to treatment for LADC patients, which needed to be validated by clinical trials of large samples.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.35.15_suppl.e20603
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 6
    Online Resource
    Online Resource
    Immunotherapy efficacy and safety of programmed cell death 1 (PD-1) versus programmed death ligand-1 (PD-L1) inhibitors in pan-cancer: A systematic review and meta-analysis.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e14113-e14113
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e14113-e14113
    Abstract: e14113 Background: Immune checkpoint inhibitors (ICIs) that target programmed cell death 1 (PD-1) and its ligand (PD-L1) have led to a paradigm shift in cancer treatment, while whether PD-1 and PD-L1 inhibitors deliver different clinical outcomes remains obscure. Here we carried out a systematic review and meta-analysis to compare the efficacy and safety profile of PD-1 and PD-L1 inhibitors in pan-cancer patients. Methods: We systematically searched PubMed, Cochrane library, and Embase from January 2000 to December 2018 for randomized controlled trials that compared PD-1/PD-L1 inhibitors with standard treatment in patients with solid tumors. We also reviewed abstracts and presentations from all major conference proceedings. Retrospective studies and trials that compared anti-PD-1/PD-L1 with other immunotherapies were excluded. The primary outcome was the difference in overall survival (OS). Studies were stratified into comparison groups upon studies mirrored with trial design and patient characteristics. Effect size in each comparison group was pooled first, the difference in overall survival was estimated, and the overall effect sizes was pooled using a random-effects model. Results: A total of 3864 publications were retrieved through initial literature search, 17 randomized controlled trials involving 9549 patients with solid tumors were included for this meta-analysis. PD-1 inhibitors exhibited significantly improved OS over PD-L1 inhibitors either in overall population (HR 0.75, 95% CI 0.64-0.87), as monotherapy (HR 0.79, 95% CI 0.65-0.96), or combination with chemotherapy (HR 0.66, 95% CI 0.53-0.82). PD-1 inhibitors also showed improved progression free survival (PFS) over PD-L1 inhibitors in overall population (HR 0.70, 95% CI 0.53-0.94). No significant difference was observed for safety profile between PD-1 inhibitors and PD-L1 inhibitors as monotherapy. PD-1 inhibitors plus chemotherapy have less Grade 3-5 adverse events than PD-L1 inhibitors plus chemotherapy (overall RR 0.84, 95% CI 0.75-0.93). Sensitivity analysis presented a satisfactory consistency of the overall estimates across these analyses. Conclusions: PD-1 inhibitors exhibited better clinical performance for survival outcome and safety profile over PD-L1 inhibitors. Future studies and explorations of the underlying mechanisms are needed for the further optimization of treatment strategies in clinical practice.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.e14113
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 7
    Online Resource
    Online Resource
    Deep analysis to inconsistent results of EGFR mutation status in tumor tissues and plasma DNA in advanced NSCLC.
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 15_suppl ( 2016-05-20), p. e20591-e20591
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. e20591-e20591
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2016.34.15_suppl.e20591
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
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  • 8
    Online Resource
    Online Resource
    EGFR variant III expression in Chinese patients with non-small cell lung cancer.
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. e18022-e18022
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e18022-e18022
    Abstract: e18022 Background: Patients with advanced squamous cell lung carcinoma (SCC), even though harboring the EGFR mutation, showed an inferior response to EGFR-TKI. The aim of this retrospective study was to determine the clinicopathologic characteristics and distribution profiles of EGFRv III in Chinese NSCLC patients, and to explore the likely relationship between EGFRv III mRNA levels and the response to EGFR-TKI. Methods: Frozen tissues were retrospectively obtained from 114 NSCLC patients who received surgery resection and 13 advanced NSCLC patients who received EGFR-TKI treatment in Peking Universuty Cancer Hospital. EGFRv III expression was detected by RT-PCR and EGFR mutation was detected by denaturing high-performance liquid chromatography (DHPLC). The association between EGFRv III and clinicopathologic features was investigated by statistical analysis. Results: frequency of EGFRv III in 114 post-surgery NSCLC patients was 7.02% (8/114), including 11.11% (6/54) in SCC and 3.64% (2/55) in adenocarcinomas (ADC). The frequency of EGFRv III expression was higher in SCC than in ADC, but the difference didn’t reach statistical significance (p = 0.269). In the subgroup of 8 EGFRv III-positive patients, 7 (87.5%) were male, 6 patients (75.0%) were smokers or former smokers,. No EGFR mutation was detected. In 13 advanced SCC patients who received treatment with EGFR-TKI, no patient harboring EGFRv III was found, and 3 patients (23.08%) were tested for EGFR mutation. Conclusions: The frequency of EGFRv III in Chinese NSCLC was low and squamous histology, smokers or former- smokers, and male gender might be related to EGFRv III and have effects exclusive of EGFR mutation.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.15_suppl.e18022
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 9
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    Online Resource
    Genomic and epigenomic profiles to distinguish pulmonary enteric adenocarcinoma from lung metastatic colorectal cancer.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e13528-e13528
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e13528-e13528
    Abstract: e13528 Background: As an extremely rare variant of lung adenocarcinoma, the diagnosis of pulmonary enteric adenocarcinoma (PEAC) remains challenging in the clinic due to shared morphological and immunohistochemical features with lung metastatic colorectal cancer (mCRC). Current differentiation of PEAC and mCRC mainly relies on clinical history and pathological examination while which still remain risks of misdiagnosis. Due to their distinct treatment regimens, effective molecular markers are essential for accurate diagnosis. However, comprehensive molecular features of PEAC is still poorly understood. Methods: We performed whole-exome sequencing and targeted bisulfite sequencing of 23 PEAC and 20 mCRC and matched normal tissue to improve molecular characterization. For DNA methylation profiling, differentially methylated regions (DMR) were analyzed by comparing PEAC with normal lung tissue and with mCRC. We also trained machine learning methods to distinguish PEAC from mCRC and validated the classifier in an independent cohort with 10 PEAC and 10 mCRC. Results: Mutations of KRAS, APC, and EGFR, alterations of chromosome arms 13q, 14q and 18p were found to be the major differential genetic alterations between PEAC and mCRC (P 〈 0.05), yet not enough to aid clinical diagnosis. For epigenomic profile, we identified 524 DMRs (false discovery rate ≤0.05) which were further reduced to 30 DMRs according to importance rank by the random forest algorithm. Based on these DMR features, we developed a diagnostic classifier that correctly classified 95.1% of patients in this discovery cohort. We further validated this predictive model in the validation cohort, with a prediction accuracy of 90.0%. We demonstrated its clinical application in two cases with difficulties to diagnosis by traditional methods. Conclusions: We have illustrated the unique genetic and methylation profiles of PEAC and mCRC. Our approach for disease classification may have a substantial impact on diagnostic precision and therapeutic decision for PEAC.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e13528
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 10
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    Online Resource
    Cytoplasmic ERß expression to predict efficacy and survival of EGFR-TKI in EGFR-mutant NSCLC.
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. e19067-e19067
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. e19067-e19067
    Abstract: e19067 Background: Estrogen receptor pathway has been reported to be interacted with epidermal growth factor receptor (EGFR) signal pathway. This study focused on the impact of intracellular ERβ localization (cytoplasmic or nuclear) on efficacy of EGFR-TKI. Methods: Tumor tissue specimens from 149 stage IV NSCLC patients treated with EGFR-TKI were analyzed using immunohistochemistry (IHC) for ER expression (ERα or β) and their associations with clinicopathological variables and clinical outcomes. Significance of cyto-ERβ expression was further examined in NSCLC cell lines. Results: The expression of ERα and ERβ was detected in 15% and 28.9% of the patients, respectively. Cyto-ERβ positive cases showed shortened PFS compared with negative ones (3.1 months vs. 7.3 months, p=0.061). In the EGFR-mutant subgroup, differences of PFS were enlarged with significant statistics (4.7 months vs. 10.9 months, p=0.042). COX’s proportional hazard model showed that female, EGFR mutation and c-ERβ status were independent predictors for PFS. PC-9 cells present ERβ in cytoplasma and nucleus. Estrodial (E2) induced PC-9 cells moderately resistant to erlotinib with a 3-fold increase of IC50, and the resistance can be reversed by ER blocker (fulvestrant) or siRNA directed to ESR2. The E2 function was accomplished by nongenomic activation (MAPK phosphorylation) caused by E2 via cyto-ERβ. Combination treatment with erlotinib and fulvestrant turned out to be far more effective than either treatment alone in PC-9 cells. Conclusions: Cyto-ERβ expression may predict relatively poor efficacy to EGFR-TKI compared with non- cyto-ERβ expression in NSCLC patients harboring EGFR mutation.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.e19067
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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