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  • American Society of Clinical Oncology (ASCO)  (23)
  • 11
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    Overall Survival in Patients With Advanced Melanoma Who Received Nivolumab Versus Investigator’s Choice Chemotherapy in CheckMate 037: A Randomized, Controlled, Open-Label Phase III Trial
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 4 ( 2018-02-01), p. 383-390
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 4 ( 2018-02-01), p. 383-390
    Abstract: Until recently, limited options existed for patients with advanced melanoma who experienced disease progression while receiving treatment with ipilimumab. Here, we report the coprimary overall survival (OS) end point of CheckMate 037, which has previously shown that nivolumab resulted in more patients achieving an objective response compared with chemotherapy regimens in ipilimumab-refractory patients with advanced melanoma. Patients and Methods Patients were stratified by programmed death-ligand 1 expression, BRAF status, and best prior cytotoxic T-lymphocyte antigen-4 therapy response, then randomly assigned 2:1 to nivolumab 3 mg/kg intravenously every 2 weeks or investigator’s choice chemotherapy (ICC; dacarbazine 1,000 mg/m 2 every 3 weeks or carboplatin area under the curve 6 plus paclitaxel 175 mg/m 2 every 3 weeks). Patients were treated until they experienced progression or unacceptable toxicity, with follow-up of approximately 2 years. Results Two hundred seventy-two patients were randomly assigned to nivolumab (99% treated) and 133 to ICC (77% treated). More nivolumab-treated patients had brain metastases (20% v 14%) and increased lactate dehydrogenase levels (52% v 38%) at baseline; 41% of patients treated with ICC versus 11% of patients treated with nivolumab received anti–programmed death 1 agents after randomly assigned therapy. Median OS was 16 months for nivolumab versus 14 months for ICC (hazard ratio, 0.95; 95.54% CI, 0.73 to 1.24); median progression-free survival was 3.1 months versus 3.7 months, respectively (hazard ratio, 1.0; 95.1% CI, 0.78 to 1.436). Overall response rate (27% v 10%) and median duration of response (32 months v 13 months) were notably higher for nivolumab versus ICC. Fewer grade 3 and 4 treatment-related adverse events were observed in patients on nivolumab (14% v 34%). Conclusion Nivolumab demonstrated higher, more durable responses but no difference in survival compared with ICC. OS should be interpreted with caution as it was likely impacted by an increased dropout rate before treatment, which led to crossover therapy in the ICC group, and by an increased proportion of patients in the nivolumab group with poor prognostic factors.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2016.71.8023
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 12
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    Crizotinib and Surgery for Long-Term Disease Control in Children and Adolescents With ALK-Positive Inflammatory Myofibroblastic Tumors
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  JCO Precision Oncology , No. 3 ( 2019-12), p. 1-11
    Details
    In: JCO Precision Oncology, American Society of Clinical Oncology (ASCO), , No. 3 ( 2019-12), p. 1-11
    Abstract: Before anaplastic lymphoma kinase (ALK) inhibitors, treatment options for ALK-positive inflammatory myofibroblastic tumors (AP-IMTs) were unsatisfactory. We retrospectively analyzed the outcome of patients with AP-IMT treated with crizotinib to document response, toxicity, survival, and features associated with relapse. METHODS The cohort comprised eight patients with AP-IMT treated with crizotinib and surgery. Outcome measures were progression-free and overall survival after commencing crizotinib, treatment-related toxicities, features associated with relapse, outcome after relapse, and outcome after ceasing crizotinib. RESULTS The median follow-up after commencing crizotinib was 3 years (range, 0.9 to 5.5 years). The major toxicity was neutropenia. All patients responded to crizotinib. Five were able to discontinue therapy without recurrence (median treatment duration, 1 year; range, 0.2 to 3.0 years); one continues on crizotinib. Two critically ill patients with initial complete response experienced relapse while on therapy. Both harbored RANBP2-ALK fusions and responded to alternative ALK inhibitors; one ultimately died as a result of progressive disease, whereas the other remains alive on treatment. Progression-free and overall survival since commencement of crizotinib is 0.75 ± 0.15% and 0.83 ± 0.15%, respectively. CONCLUSION We confirm acceptable toxicity and excellent disease control in patients with AP-IMT treated with crizotinib, which may be ceased without recurrence in most. Relapses occurred in two of three patients with RANBP2-ALK translocated IMT, which suggests that such patients require additional therapy.
    Type of Medium: Online Resource
    ISSN: 2473-4284
    URL: Article
    DOI: 10.1200/PO.18.00297
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
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  • 13
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    Phase 1 study of selinexor plus mitoxantrone, etoposide, and cytarabine in acute myeloid leukemia.
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 15_suppl ( 2018-05-20), p. 7048-7048
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. 7048-7048
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2018.36.15_suppl.7048
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 14
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    Efficacy and Safety Outcomes in Patients With Advanced Melanoma Who Discontinued Treatment With Nivolumab and Ipilimumab Because of Adverse Events: A Pooled Analysis of Randomized Phase II and III Trials
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 34 ( 2017-12-01), p. 3807-3814
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 34 ( 2017-12-01), p. 3807-3814
    Abstract: Approximately 40% of patients with advanced melanoma who received nivolumab combined with ipilimumab in clinical trials discontinued treatment because of adverse events (AEs). We conducted a retrospective analysis to assess the efficacy and safety of nivolumab plus ipilimumab in patients who discontinued treatment because of AEs. Methods Data were pooled from phase II and III trials of patients who received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, every 3 weeks for four doses, followed by nivolumab monotherapy 3 mg/kg every 2 weeks (N = 409). Efficacy was assessed in all randomly assigned patients who discontinued because of AEs during the induction phase (n = 96) and in those who did not discontinue because of AEs (n = 233). Safety was assessed in treated patients who discontinued because of AEs (n = 176) at any time and in those who did not discontinue because of AEs (n = 231). Results At a minimum follow-up of 18 months, median progression-free survival was 8.4 months for patients who discontinued treatment because of AEs during the induction phase and 10.8 months for patients who did not discontinue because of AEs ( P = .97). Median overall survival had not been reached in either group ( P = .23). The objective response rate was 58.3% for patients who discontinued because of AEs during the induction phase and 50.2% for patients who did not discontinue. The vast majority of grade 3 or 4 AEs occurred during the induction phase, with most resolving after appropriate management. Conclusion Efficacy outcomes seemed similar between patients who discontinued nivolumab plus ipilimumab treatment because of AEs during the induction phase and those who did not discontinue because of AEs. Therefore, even after discontinuation, many patients may continue to derive benefit from combination therapy.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2017.73.2289
    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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  • 15
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    Analysis of MET exon 14skippingmutations in non–small cell lung cancer (NSCLC) by histology and specific mutation.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 9119-9119
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 9119-9119
    Abstract: 9119 Background: MET exon 14 skipping mutations (METex14) join a growing list of viable therapeutic targets in advanced NSCLC. Several unique features distinguish METex14 from other established targets. METex14 has been characterized as a tumor-agnostic genomic alteration, though most frequently reported in lung adenocarcinoma. However, METex14 represents a family of mutations (mt), not a single alteration, and there is notable heterogeneity in histology. The degree and significance of heterogeneity within METex14 have not been well characterized. Methods: NSCLC tissue samples were analyzed with DNA-based next-generation sequencing (NGS; 592 genes, NextSeq) or whole-exome sequencing (NovaSeq), RNA-based whole transcriptome sequencing (WTS, NovaSeq), and immunohistochemistry (IHC) at Caris Life Sciences (Phoenix, AZ). PD-L1 expression utilized the 22C3 clone (Dako); TMB-high was defined as ≥ 10 mt/Mb. Wilcoxon or Fisher’s exact were used to determine statistical significance (p without and q with multi comparison correction). Immune cell fraction (QuanTiseq) and pathway analysis (ssGSEA) were informed by WTS analysis. Results: A total of 440 METex14 cases were identified: 49 (11.1%) with squamous histology, 381 (86.6%) with non-squamous histology, and 10 (0.2%) with adenosquamous histology. A total of 147 distinct METex14 mutations were detected. The most common METex14 mutations were D1028H (8.4%), D1028N (7.0%), c.3082+2T 〉 C (5.7%), D1028Y (5.2%), and c.3082+1G 〉 A (4.5%). Co-mutations in TP53 were common (43.9%) but varied by specific METex14 mutation; TP53 co-mutations were observed in 53.9% of c.3082+3A 〉 T but only 21.1% of c.3082+1G 〉 T. Among all METex14 cases, 8.6% were TMB-high, but this varied by specific mutation with a median TMB of 2 mt/Mb in MET c.3082+2T 〉 A and a median of 7 mt/Mb in MET c.3082+1G 〉 C (q 〈 0.05). PD-L1 expression ≥ 1% was present in 82.2% of METex14 samples but also varied by specific METex14 mutation with a median PD-L1 tumor proportion score (TPS) of 97.5% in MET c.3082+1G 〉 C and a median TPS of 0% in MET c.3082+3A 〉 G (q 〈 0.05). Co-mutations varied by histology: in squamous METex14, 90.4% had TP53 mt (p 〈 0.001), 17.9% had KMT2D mt (p 〈 0.05), and 10.7% had PIK3CA mt (p 〈 0.05), while in non-squamous METex14, 60.7% had TP53 mt, 2.7% had KMT2D mt, and 4.3% had PIK3CA mt. Survival was numerically shorter in squamous METex14 NSCLC compared to non-squamous (HR 1.22, p = 0.47, mOS 336 vs.1106 days). Conclusions: There is significant heterogeneity within METex14 NSCLC with differences in co-mutations, TMB, and PD-L1 expression noted among different METex14 mutations. While METex14 is detected in both squamous and non-squamous NSCLC, there are differences in enrichment of oncogenic pathways. The clinical impact of these differences warrants further investigation.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.9119
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 16
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    Age as a factor in the molecular landscape and the tumor-microenvironmental signature of osteosarcoma.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 11525-11525
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 11525-11525
    Abstract: 11525 Background: Osteosarcoma (OS) incidence is characterized by a bimodal age distribution, with peaks in early adolescence and in adults 〉 65 years of age. In contrast to adolescents, OS in adults is frequently considered as a secondary neoplasm (i.e., transformation of Paget´s disease of the bone, radiation induced). Yet, the literature is scarce regarding the impact of age on the molecular landscape of OS. Herein, we sought to explore the association between age and the genomic profile as well as the tumor immune microenvironment (TME) in a large cohort of OS patients. Methods: 208 specimens were centrally analysed at the Caris Life Sciences laboratory with DNA seq (NextSeq, 592 gene panel or NovaSeq, whole-exome sequencing), RNA seq (Archer fusion panel or whole-transcriptome sequencing) and immunohistochemistry (IHC). RNA deconvolution and differential expression analyses were performed using the Microenvironment Cell Populations counter method for quantification of immune cell populations and gene expression profiling. The cohort was stratified into three distinct age groups ( 〈 25 years [n = 83], 25-45 years [n = 58] , 〉 45 years [67]). Results: Overall, the most frequently detected mutations were in TP53 (37%), RB1 (13%), ATRX (9%), TERT (6%), PTEN (5%), PIK3CA (4%) and KMT2D (3%). Copy number alterations were most frequently detected in CDK4 (12%), LRIG3 (11%), FLCN (11%), MDM2 (9%), CCND3 (9%), VEGFA (8%), TFEB (8%). Interestingly, age-based stratification revealed an increased frequency of FLCN (19.7 vs 4.7%, p 〈 0.01), CCND3 (13.9 vs 3.1%, p 〈 0.05), and HSP90AB1 (11.3 vs 0.0%, p 〈 0.01), alterations in patients 〈 25 years compared to 〉 45 years. TME analysis revealed that patients 〉 45 years have decreased B-cell abundance compared to patients 〈 25 years (2.9-fold decrease, p 〈 0.05) and 25-45 years (4.8-fold decrease, p 〈 0.05). Although not statistically significant, median transcriptional expression of PD-L1 was numerically increased in patients 〉 45 years (1.8-fold compared to 25-45 years, p = 0.17; 2.0-fold compared to 〈 25 years, p = 0.27), which was consistent with increasing rates of IHC PD-L1 expression with age (5.3%, 9.4%, and 17.5%, respectively, p = 0.06). Conclusions: To the best of our knowledge, this study represents the largest cohort of molecularly characterized OS. Age-associated differences in the genetic landscape and TME composition, including increased gene amplifications observed in younger patients and decreased B-cell abundance in older patients, might suggest fundamental underlying molecular and biological differences.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.11525
    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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  • 17
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    Type of prior genotoxic insult determines the genomic characteristics of therapy-related acute myeloid leukemia.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 7515-7515
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 7515-7515
    Abstract: 7515 Background: Therapy-related AML (tAML) is a long-term complication of cytotoxic cancer therapy. It is characterized by adverse genetics and inferior survival outcomes when compared to de novo AML. A proposed mechanism in tAML pathogenesis includes treatment-induced selection of clones harboring pre-existing mutations (i.e. clonal hematopoiesis, CH). We hypothesize that genotoxic therapies used to treat prior malignancy drive leukemogenesis through different mechanisms leading to unique clonal compositions. Methods: AML patients (pts) treated at The Ohio State University between 2015-2018 were included. Genetic profiling was performed using Miseq Illumina platform with a 49-gene targeted sequencing panel at our clinical laboratory. Results: We studied 337 AML pts (Table), of whom 53% had smoking history. Mutations involving ASXL1 were more common in smokers vs non-smokers (14% vs 5.8%, p= .001), while JAK2 mutations were more common in non-smokers (8% vs 1.2%, p= .003). Regarding specific genotoxic therapies and mutations in tAML, we investigated common CH-associated mutations including DNMT3A, TET2, and ASXL1 (DTA mutations). In tAML pts, those exposed to radiotherapy experienced a higher frequency of DTA (52% vs 27%, p= .05), NPM1 (21% vs 0%, p= .002), and SRSF2 (15% vs 0%, p= .01) mutations, and conversely, a lower incidence of TP53 mutations (21% vs 46%, p= .04). Pts with history of cytotoxic chemotherapy had a lower incidence of DTA mutations, including those who received platinum agents (8% vs 49%, p= .005) and taxanes (7% vs 52%, p 〈 .001), but had a higher incidence of TP53 mutations (75% vs 25%, p 〈 .001 for platinum; 53% vs 25%, p= .04 for taxanes). Similarly, alkylators and anthracyclines were associated with lower incidence of DNMT3A (0% vs 20%, p= .009) and ASXL1 (0% vs 12.5%, p= .04) mutations. Conclusions: Different genotoxic agents demonstrate unique effects in leukemia development. Our data suggest that CH clones with DTA mutations may be enriched with smoking and radiotherapy, while cytotoxic chemotherapy may confer a higher incidence of TP53 mutations. Given the adverse prognosis of TP53 mutated AML, identification of pre-existing CH clones might influence treatment selection in solid tumor pts receiving anticancer therapy. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.7515
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 18
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    Updated molecular analysis of MET exon 14skippingmutations ( MET ex14) in non-small cell lung cancer (NSCLC).
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 9095-9095
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 9095-9095
    Abstract: 9095 Background: METex14 is a heterogeneous family of mutations (mt) in NSCLC that can be effectively treated with approved targeted agents. Unlike some other drivers in NSCLC, METex14 occurs in both squamous and adenocarcinoma histology and in both smokers and non-smokers. Here, we present updated results from analysis of a large dataset to characterize the mutational landscape within METex14 NSCLC. Methods: NSCLC tissue samples were analyzed with DNA-based next-generation sequencing (NGS; 592 genes, NextSeq) or whole-exome sequencing (NovaSeq), RNA-based whole transcriptome sequencing (WTS, NovaSeq), and PD-L1 immunohistochemistry (Dako 22C3) at Caris Life Sciences (Phoenix, AZ). METex14 was detected by WTS. TMB-high was defined as ≥ 10 mt/Mb. Chi-square, Fisher’s exact or Mann-Whitney U tests were used to determine statistical significance and corrected for multiple hypothesis testing (q 〈 0.05). Immune cell estimates (quanTIseq) and pathway analysis (ssGSEA) were informed by WTS analysis. Results: A total of 711 METex14 cases were detected with 288 distinct METex14 mt. By histology, 79 (11.1%) were squamous (Sq), 478 (67.23%) were nonsquamous (nSq), and 24 (3.23%) were adenosquamous. The most common METex14 mt were D1028H (8.1%), D1028N (7.8%), c.3082+2T 〉 C (5.0%), D1028Y (4.6%), and c.3082+1G 〉 T (4.4%). Co-mutated TP53 was common (43.4%) but varied by specific METex14 mt, observed in 60.0% of MET c.3082+3A 〉 G vs 16.7% of MET G344R . Co-amplified CDK4 was found in 9.3%, with 42.9% in MET c.2924-1G 〉 A vs 6.7% in MET c.3802+1G 〉 T (p 〈 0.05). High TMB was seen in 9%; median TMB ranged from 2 mt/Mb in MET c.3082+2T 〉 A to 6.5 mt/Mb in MET c.3082+2T 〉 G (p 〈 0.05). PD-L1 ≥ 1% was seen in 80.8% compared to 56.2% in METex14-WT(p 〈 0.05), and median PD-L1 tumor proportion score (TPS) ranged from 0% in MET G344R to 75% in MET c.3082+2T 〉 A (p 〈 0.05). Co-mutations varied by histology: in Sq-NSCLC, 18.18% had TP53 mt (q 〈 0.05), 8.97% had POT1 mt (p 〈 0.05), 6.06% had TERT mt (p 〈 0.05), 5.13% CASP8 mt (q 〈 0.05), and 2.53% RNF43 mt (p 〈 0.05), while in nSq-NSCLC, 45.51% had TP53 mt, 3.38% had POT1 mt, 0.87% had TERT mt, and 0% in CASP8 and RNF43 mt. Smoking status was available for 120 cases: 88% were smokers and 12% were nonsmokers. Wnt, Hedgehog, and Notch signaling were enriched in nSq (q 〈 0.05) while upregulation of KRAS signaling, Epithelial-Mesenchymal Transition, and angiogenesis pathways were enriched in smokers with METext14 NSCLC (q 〈 0.2). Higher estimates of neutrophils and lower estimates of M2 macrophages, NK cells, and CD8+ T-cells were observed in Sq-NSCLC. PD-L1, PD-1, HAVCR-2, IDO-1 and IFN-γ expression were higher in nSq than Sq-NSCLC (q 〈 0.05). Conclusions: METex14 NSCLC is highly heterogenous, with variations in co-mutation, TMB, and PD-L1 expression. Although Sq- and nSq-NSCLC harbor METex14, the enrichment of oncogenic pathways and infiltrating immune cells differ between histology and smoking history.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.9095
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 19
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    A randomized phase II study of erdafitinib (ERDA) versus intravesical chemotherapy (IC) in patients with high-risk nonmuscle invasive bladder cancer (HR-NMIBC) with FGFR mutations or fusions, who recurred after Bacillus Calmette-Guérin (BCG) therapy.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 6_suppl ( 2020-02-20), p. TPS603-TPS603
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 6_suppl ( 2020-02-20), p. TPS603-TPS603
    Abstract: TPS603 Background: ERDA, an oral pan-FGFR inhibitor, is approved by the US FDA for metastatic urothelial carcinoma (mUC) with susceptible FGFR3 or FGFR2 gene alterations and progressed on/ or after at least 1 line of prior platinum-containing chemotherapy (PCC) including within 12 months of neoadjuvant/adjuvant PCC. 1 Around 40% of patients with bladder cancer present with HR-NMIBC. First-line BCG therapy fails in 30-40% of patients and subsequent treatment options are limited. This study is designed to evaluate recurrence-free survival (RFS) following treatment with ERDA vs IC in patients with FGFR positive HR-NMIBC who recurred after BCG therapy. Methods: This is an open-label, multicenter, randomized, phase 2, safety and efficacy study of ERDA in adults with histologically confirmed HR-NMIBC and FGFR mutations or fusions. Inclusion criteria: ECOG status ≤1, adequate bone marrow, liver, renal function, and ineligibility for or declining cystectomy, with no history of prior FGFR inhibitors. Patients will be enrolled into 1 of 3 cohorts. Cohort 1 (n=240): high-grade disease Ta/T1 lesion (papillary only) with disease recurrence after BCG therapy will be randomized to ERDA or IC (investigator choice: gemcitabine or mitomycin C); Cohort 2 (n=20): carcinoma in situ (CIS) with/without papillary disease to receive ERDA monotherapy; Cohort 3 (n=20): marker lesion study in patients with intermediate-risk papillary disease only to receive ERDA monotherapy. Dose will be maintained at 8 mg, up-titrated to 9 mg, or withheld based on phosphate levels. Primary endpoint: Cohort 1- RFS; Secondary endpoints: Cohort 1 - time to progression and disease worsening, disease-specific survival (invasive bladder cancer), overall survival, RFS rate at 6, 12, 24 months, and RFS on subsequent anticancer therapy (RFS2). An IDMC will be commissioned for Cohort 1. Exploratory endpoints: Cohort 2- complete response (CR) rate at 6 months; Cohort 3- CR in marker lesion. Patients will be enrolled at sites in ~14 countries. EudraCT: 2019-002449-39. Loriot Y et al. N Engl J Med. 2019;381:338-48. Clinical trial information: 2019-002449-39.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.6_suppl.TPS603
    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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  • 20
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    Diagnostic utility of bronchoscopy in newly diagnosed acute leukemia patients.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e19510-e19510
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e19510-e19510
    Abstract: e19510 Background: Over 40% of newly diagnosed acute leukemia patients receiving induction therapy develop acute respiratory failure. Bronchoscopy is a valuable tool for evaluating airway disease, but its diagnostic yield in this setting has not been fully explored. Methods: We performed a retrospective chart review of 75 newly diagnosed acute leukemia patients who had bronchoscopies. Data recorded prior to bronchoscopy included age, diagnosis, induction treatment regimen, chest imaging, assisted ventilation, duration of neutropenia and antibiotic therapy and microbiological studies. Bronchoalveolar lavage (BAL) cultures were sorted by organism, as well as by other pathologic findings. The primary outcome was antibiotic change supported by culture data. Results: The study population is summarized in the table. Induction regimen backbones included 7+3 (51), 7+4+ATRA (2), decitabine (12), hyperCVAD (2), AYA (3), other (1) and none (4); 18 patients were treated on clinical trial. Average days of neutropenia was 10.92 and average days of antibiotic therapy was 10.57. Thirty-eight patients had chest infiltrates, 11 received NIPPV, and 17 were mechanically ventilated. We identified 24 patients with +BAL studies. Of these, 37.5% (9) had + blood, urine or sputum studies before bronchoscopy, but only 3 had cultures positive for the same organism as the BAL. Of 51 patients with –BAL studies, 33.3% (17) had prior negative cultures. Infections were most commonly bacterial (15, 62.5%), followed by viral (5, 20.8%) and fungal (4, 16.7%). The most common organisms were rhinovirus, vancomycin sensitive Enterococcus (4, 16.7% each) followed by VRE, Candida albicans and MRSA (2, 8.3% each). Five patients (6.7%) had alveolar hemorrhage. Of the 24 patients with +BAL cultures, bronchoscopy findings supported changing antibiotics in 18. In contrast, antibiotics were changed in 16 patients without +BAL cultures. Conclusions: We investigated the utility of bronchoscopy on AL patients during their initial admission. BAL cultures were positive in 32% of newly diagnosed AL patients undergoing bronchoscopy. However, +BAL cultures identified a new organism in 87.5% and guided antibiotic therapy in 75% of these patients. Further studies will be needed to establish predictors of bronchoscopy findings in this patient population. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e19510
    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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