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  • American Society of Clinical Oncology (ASCO)  (5)
  • Le Chevalier, Thierry  (5)
  • 1
    Online Resource
    Online Resource
    Pooled Analysis of the Prognostic and Predictive Effects of TP53 Comutation Status Combined With KRAS or EGFR Mutation in Early-Stage Resected Non–Small-Cell Lung Cancer in Four Trials of Adjuvant Chemotherapy
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 18 ( 2017-06-20), p. 2018-2027
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 18 ( 2017-06-20), p. 2018-2027
    Abstract: Our previous work evaluated individual prognostic and predictive roles of TP53, KRAS, and EGFR in non–small-cell lung cancer (NSCLC). In this analysis, we explore the prognostic and predictive roles of TP53/KRAS and TP53/EGFR comutations in randomized trials of adjuvant chemotherapy versus observation. Patients and Methods Mutation analyses (wild-type [WT] and mutant) for TP53, KRAS, and EGFR were determined in blinded fashion in multiple laboratories. Primary and secondary end points of pooled analysis were overall survival and disease-free survival. We evaluated the role of TP53/KRAS comutation in all patients and in the adenocarcinoma subgroup as well as the TP53/EGFR comutation in adenocarcinoma only through a multivariable Cox proportional hazards model stratified by trial. Results Of 3,533 patients with NSCLC, 1,181 (557 deaths) and 404 (170 deaths) were used for TP53/KRAS and TP53/EGFR analyses. For TP53/KRAS mutation status, no prognostic effect was observed ( P = .61), whereas a borderline predictive effect ( P = .04) was observed with a deleterious effect of chemotherapy with TP53/KRAS comutations versus WT/WT (hazard ratio, 2.49 [95% CI, 1.10 to 5.64]; P = .03). TP53/EGFR comutation in adenocarcinoma was neither prognostic ( P = .83), nor significantly predictive ( P = .86). Similar results were observed for both groups for disease-free survival. Conclusion We could identify no prognostic effect of the KRAS or EGFR driver and TP53 tumor suppressor comutation. Our observation of a potential negative predictive effect of TP53/KRAS comutation requires validation.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2016.71.2893
    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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  • 2
    Online Resource
    Online Resource
    Pooled Analysis of the Prognostic and Predictive Effects of KRAS Mutation Status and KRAS Mutation Subtype in Early-Stage Resected Non–Small-Cell Lung Cancer in Four Trials of Adjuvant Chemotherapy
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 17 ( 2013-06-10), p. 2173-2181
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 17 ( 2013-06-10), p. 2173-2181
    Abstract: We undertook this analysis of KRAS mutation in four trials of adjuvant chemotherapy (ACT) versus observation (OBS) to clarify the prognostic/predictive roles of KRAS in non–small-cell lung cancer (NSCLC). Methods KRAS mutation was determined in blinded fashion. Exploratory analyses were performed to characterize relationships between mutation status and subtype and survival outcomes using a multivariable Cox model. Results Among 1,543 patients (763 OBS, 780 ACT), 300 had KRAS mutations (codon 12, n = 275; codon 13, n = 24; codon 14, n = 1). In OBS patients, there was no prognostic difference for overall survival for codon-12 (mutation v wild type [WT] hazard ratio [HR] = 1.04; 95% CI, 0.77 to 1.40) or codon-13 (HR = 1.01; 95% CI, 0.47 to 2.17) mutations. No significant benefit from ACT was observed for WT-KRAS (ACT v OBS HR = 0.89; 95% CI, 0.76 to 1.04; P = .15) or codon-12 mutations (HR = 0.95; 95% CI, 0.67 to 1.35; P = .77); with codon-13 mutations, ACT was deleterious (HR = 5.78; 95% CI, 2.06 to 16.2; P 〈 .001; interaction P = .002). There was no prognostic effect for specific codon-12 amino acid substitution. The effect of ACT was variable among patients with codon-12 mutations: G12A or G12R (HR = 0.66; P = .48), G12C or G12V (HR = 0.94; P = .77) and G12D or G12S (HR = 1.39; P = .48; comparison of four HRs, including WT, interaction P = .76). OBS patients with KRAS-mutated tumors were more likely to develop second primary cancers (HR = 2.76, 95% CI, 1.34 to 5.70; P = .005) but not ACT patients (HR = 0.66; 95% CI, 0.25 to 1.75; P = .40; interaction, P = .02). Conclusion KRAS mutation status is not significantly prognostic. The potential interaction in patients with codon-13 mutations requires validation. At this time, KRAS status cannot be recommended to select patients with NSCLC for ACT.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2012.48.1390
    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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  • 3
    Online Resource
    Online Resource
    Prognostic Effect of Tumor Lymphocytic Infiltration in Resectable Non–Small-Cell Lung Cancer
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 11 ( 2016-04-10), p. 1223-1230
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 11 ( 2016-04-10), p. 1223-1230
    Abstract: Tumor lymphocytic infiltration (TLI) has differing prognostic value among various cancers. The objective of this study was to assess the effect of TLI in lung cancer. Patients and Methods A discovery set (one trial, n = 824) and a validation set (three trials, n = 984) that evaluated the benefit of platinum-based adjuvant chemotherapy in non–small-cell lung cancer were used as part of the LACE-Bio (Lung Adjuvant Cisplatin Evaluation Biomarker) study. TLI was defined as intense versus nonintense. The main end point was overall survival (OS); secondary end points were disease-free survival (DFS) and specific DFS (SDFS). Hazard ratios (HRs) and 95% CIs associated with TLI were estimated through a multivariable Cox model in both sets. TLI-histology and TLI-treatment interactions were explored in the combined set. Results Discovery and validation sets with complete data included 783 (409 deaths) and 763 (344 deaths) patients, respectively. Median follow-up was 4.8 and 6 years, respectively. TLI was intense in 11% of patients in the discovery set compared with 6% in the validation set (P 〈 .001). The prognostic value of TLI in the discovery set (OS: HR, 0.56; 95% CI, 0.38 to 0.81; P = .002; DFS: HR, 0.59; 95% CI, 0.42 to 0.83; P = .002; SDFS: HR, 0.56; 95% CI, 0.38 to 0.82; P = .003) was confirmed in the validation set (OS: HR, 0.45; 95% CI, 0.23 to 0.85; P = .01; DFS: HR, 0.44; 95% CI, 0.24 to 0.78; P = .005; SDFS: HR, 0.42; 95% CI, 0.22 to 0.80; P = .008) with no heterogeneity across trials (P ≥ .38 for all end points). No significant predictive effect was observed for TLI (P ≥ .78 for all end points). Conclusion Intense lymphocytic infiltration, found in a minority of tumors, was validated as a favorable prognostic marker for survival in resected non–small-cell lung cancer.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2015.63.0970
    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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  • 4
    Online Resource
    Online Resource
    Role of the total mutation burden (TMB) and tumor-infiltrating lymphocytes (TILs) on the development of second primary cancer after complete resection of non-small cell lung cancer (NSCLC).
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e21092-e21092
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e21092-e21092
    Abstract: e21092 Background: Risk of developing SPC after complete surgical resection of NSCLC has been reported to be 3-6% per person-year. We hypothesized that genomic instability, as assessed by high TMB, and the absence of TILs in the primary tumor might be associated with SPC. Methods: The LACE [Lung Adjuvant Cisplatin Evaluation])-BIO database was used, which includes 3 randomized trials. TMB and TILs were analyzed on FFPE specimens. TMB was categorized into tertiles (high 〉 7.8 mutations/MB, moderate i.e. 〉 4 and 〈 = 7.8, low 〈 4) and TILs as marked vs. other. Associations on competing time-to-event endpoints (SPC, and death without developing SPC) were evaluated using the Fine and Gray model stratified by trail and adjusted on treatment, age, gender, tumor stage, nodal stage, histology, performance status and surgery type. Results: TMB and TILs assessments were available for 879 patients without missing clinical covariates; 85 patients had marked TILs. During follow-up, 47 SPCs had been observed and 392 deaths without developing SPC. Regarding TMB, a significant association was found between low TMB and death without SPC (sub-distribution hazard ratio SHR = 1.36(1.06-1.74), see Table), suggesting a higher risk of death without SPC among patient with low TMB compared to those with moderate TMB; no strong effect was observed for SPC. Regarding TILs, a trend was observed between marked TILS and a lower risk of death (SHR = 0.70 [0.47-1.04]) but to a lesser extent for SPC (SHR = 0.80 [0.28-2.28] ). Conclusions: This is the first study of the effect of genomic instability (measured by TMB) and host immune response (measured by TILs) in completely resected NSCLC on competing events of SPC and death, suggesting associations between TMB, TILs and death-without-SPC . There was no statistically significant association with SPC. However, the number of SPCs was small; these findings requires validation in other early stage lung cancer cohorts. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e21092
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 5
    Online Resource
    Online Resource
    Prognostic and predictive effect of KRAS gene copy number and mutation status in early stage non-small cell lung cancer (NSCLC) patients.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e21080-e21080
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e21080-e21080
    Abstract: e21080 Background: The prognostic and predictive role of KRAS mutations and gene copy number aberrations (CNA) in early stage NSCLC is unclear. In this study, we characterize the prognostic effect of KRAS mutation status and concomitant CN gain in early stage NSCLC, and determine the ability to predict survival benefit from adjuvant chemotherapy. We hypothesize that concomitant KRAS mutations and CN gain will be prognostic of worse survival compared to KRAS mutations alone. Methods: Clinical and genomic data from The LACE (Lung Adjuvant Cisplatin Evaluation)-BIO consortium was utilized. CNA were categorized as Gain or Neutral (Neut)/Loss; mutation status was defined as wild type (WT) or mutant (MUT). WT+Neut/Loss (reference), WT+Gain, MUT+Gain and MUT+Neut/Loss groups were compared in all patients and the adenocarcinoma subgroup. Primary endpoint was lung-cancer-specific survival (LCSS); secondary endpoints were DFS and OS. Survival curves were assessed using Kaplan-Meier and log-rank tests. Concomitant KRAS CNA and mutation status was correlated to endpoints using a Cox proportional hazards model stratified by trial and adjusted for treatment, age, gender, histology, WHO performance status, surgery type, tumor and nodal stage. A treatment-by-variable interaction was added to evaluate predictive effect. Results: 946 (399 adenocarcinoma) patients had complete KRAS mutation, CNA and clinical data: 41 (30) MUT+Gain, 145 (99) MUT+Neut/Loss, 125 (16) WT+Gain, 635 (254) WT+Neut/Loss. There was a negative prognostic effect of KRAS MUT+Neut/Loss for LCSS (HR = 1.32 [1.01-1.71]) on univariable analysis, and to a lesser extent after adjusting for covariates (HR = 1.28 [0.97-1.68] ). A similar non-significant trend was observed in KRAS MUT+Gain patients for LCSS (HR = 1.34 [0.83-2.17]), DFS (HR = 1.34 [0.86-2.09] ) and OS (HR = 1.59 [0.99-2.54]). There was no significant predictive effect in the overall population; however, a potential predictive effect of KRAS for OS was seen in the adenocarcinoma subgroup (interaction p = 0.046). KRAS MUT+Gain was associated with a beneficial effect of chemotherapy on DFS (HR = 0.33 [0.11-0.99] , p = 0.048), with a non-significant trend also seen for LCSS (HR = 0.41 [0.13-1.33]) and OS (HR = 0.40 [0.13-1.26] ). Conclusions: A small prognostic effect of KRAS mutation was identified for LCSS. A potential predictive effect of concomitant KRAS mutation status and CNA was observed for DFS in adenocarcinoma patients. These results could be driven by the small number of patients and require further validation.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e21080
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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