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  • American Society of Clinical Oncology (ASCO)  (4)
  • 1
    Online Resource
    Online Resource
    Phase II Trial of Dabrafenib Plus Trametinib in Relapsed/Refractory BRAF V600–Mutant Pediatric High-Grade Glioma
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO)
    Abstract: BRAF V600 mutation is detected in 5%-10% of pediatric high-grade gliomas (pHGGs), and effective treatments are limited. In previous trials, dabrafenib as monotherapy or in combination with trametinib demonstrated activity in children and adults with relapsed/refractory BRAF V600–mutant HGG. METHODS This phase II study evaluated dabrafenib plus trametinib in patients with relapsed/refractory BRAF V600–mutant pHGG. The primary objective was overall response rate (ORR) by independent review by Response Assessment in Neuro-Oncology criteria. Secondary objectives included ORR by investigator determination, duration of response (DOR), progression-free survival, overall survival (OS), and safety. RESULTS A total of 41 pediatric patients with previously treated BRAF V600–mutant HGG were enrolled. At primary analysis, median follow-up was 25.1 months, and 51% of patients remained on treatment. Sixteen of 20 discontinuations were due to progressive disease in this relapsed/refractory pHGG population. Independently assessed ORR was 56% (95% CI, 40 to 72). Median DOR was 22.2 months (95% CI, 7.6 months to not reached [NR]). Fourteen deaths were reported. Median OS was 32.8 months (95% CI, 19.2 months to NR). The most common all-cause adverse events (AEs) were pyrexia (51%), headache (34%), and dry skin (32%). Two patients (5%) had AEs (both rash) leading to discontinuation. CONCLUSION In relapsed/refractory BRAF V600–mutant pHGG, dabrafenib plus trametinib improved ORR versus previous trials of chemotherapy in molecularly unselected patients with pHGG and was associated with durable responses and encouraging survival. These findings suggest that dabrafenib plus trametinib is a promising targeted therapy option for children and adolescents with relapsed/refractory BRAF V600–mutant HGG.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.23.00558
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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    Online Resource
  • 2
    Online Resource
    Online Resource
    Prognostic Significance of ASXL1 Mutations in Patients With Myelodysplastic Syndromes
    American Society of Clinical Oncology (ASCO) ; 2011
    In:  Journal of Clinical Oncology Vol. 29, No. 18 ( 2011-06-20), p. 2499-2506
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 29, No. 18 ( 2011-06-20), p. 2499-2506
    Abstract: To study the incidence and prognostic impact of mutations in Additional sex comb-like 1 (ASXL1) in a large cohort of patients with myelodysplastic syndrome (MDS). Patients, Materials, and Methods Overall, 193 patients with MDS and 65 healthy volunteers were examined for ASXL1 mutations by direct sequencing and for expression levels of ASXL1. The prognostic impact of ASXL1 mutation and expression levels was evaluated in the context of other clinical and molecular prognostic markers. Results Mutations in ASXL1 occurred with a frequency of 20.7% in MDS (n = 40 of 193) with 70% (n = 28) of mutations being frameshift mutations and 30% (n = 12) being heterozygous point mutations leading to translational changes. ASXL1 mutations were correlated with an intermediate-risk karyotype (P = .002) but not with other clinical parameters. The presence of ASXL1 mutations was associated with a shorter overall survival for frameshift and point mutations combined (hazard ratio [HR], 1.744; 95% CI, 1.08 to 2.82; P = .024) and for frameshift mutations only (HR, 2.06; 95% CI, 1.21 to 3.50; P = .008). ASXL1 frameshift mutations were associated with a reduced time to progression of acute myeloid leukemia (AML; HR 2.35; 95% CI, 1.17 to 4.74; P = .017). In multivariate analysis, when considering karyotype, transfusion dependence, and IDH1 mutation status, ASXL1 frameshift mutations remained an independent prognostic marker in MDS (overall survival: HR, 1.85; 95% CI, 1.03 to 3.34; P = .040; time to AML progression: HR, 2.39; 95% CI, 1.12 to 5.09; P = .024). Conclusion These results suggest that ASXL1 mutations are frequent molecular aberrations in MDS that predict an adverse prognostic outcome. Screening of patients for ASXL1 mutations might be useful for clinical risk stratification and treatment decisions in the future.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2010.33.4938
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2011
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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    Online Resource
  • 3
    Online Resource
    Online Resource
    Combined Molecular and Clinical Prognostic Index for Relapse and Survival in Cytogenetically Normal Acute Myeloid Leukemia
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 15 ( 2014-05-20), p. 1586-1594
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 15 ( 2014-05-20), p. 1586-1594
    Abstract: Cytogenetically normal (CN) acute myeloid leukemia (AML) is the largest and most heterogeneous cytogenetic AML subgroup. For the practicing clinician, it is difficult to summarize the prognostic information of the growing number of clinical and molecular markers. Our purpose was to develop a widely applicable prognostic model by combining well-established pretreatment patient and disease characteristics. Patients and Methods Two prognostic indices for CN-AML (PINA), one regarding overall survival (OS; PINA OS ) and the other regarding relapse-free survival (RFS; PINA RFS ), were derived from data of 572 patients with CN-AML treated within the AML Cooperative Group 99 study ( www.aml-score.org ). Results On the basis of age (median, 60 years; range, 17 to 85 years), performance status, WBC count, and mutation status of NPM1, CEBPA, and FLT3-internal tandem duplication, patients were classified into the following three risk groups according to PINA OS and PINA RFS : 29% of all patients and 32% of 381 responding patients had low-risk disease (5-year OS, 74%; 5-year RFS, 55%); 56% of all patients and 39% of responding patients had intermediate-risk disease (5-year OS, 28%; 5-year RFS, 27%), and 15% of all patients and 29% of responding patients had high-risk disease (5-year OS, 3%; 5-year RFS, 5%), respectively. PINA OS and PINA RFS stratified outcome within European LeukemiaNet genetic groups. Both indices were confirmed on independent data from Cancer and Leukemia Group B/Alliance trials. Conclusion We have developed and validated, to our knowledge, the first prognostic indices specifically designed for adult patients of all ages with CN-AML that combine well-established molecular and clinical variables and that are easily applicable in routine clinical care. The integration of both clinical and molecular markers could provide a basis for individualized patient care through risk-adapted therapy of CN-AML.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2013.52.3480
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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  • 4
    Online Resource
    Online Resource
    The prognostic significance of early molecular and cytogenetic response for long-term progression-free and overall survival in imatinib-treated chronic myeloid leukemia (CML).
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 15_suppl ( 2012-05-20), p. 6510-6510
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 6510-6510
    Abstract: 6510 Background: In the face of competing first line treatment options for CML early prediction of prognosis on imatinib is desirable to assure favorable survival or otherwise consider the use of an alternative therapy. We sought to evaluate the prognostic impact of early response landmarks. Methods: A total of 1,303 newly diagnosed imatinib-treated patients (pts) from the randomized CML Study IV were investigated to correlate molecular and cytogenetic response at 3 and 6 months with progression-free and overall survival (PFS, OS). Median follow-up was 4.7 years (range 0-9). The BCR-ABL expression was determined by quantitative RT-PCR and standardized according to the international scale (BCR-ABL IS ). The proportion of Philadelphia-chromosome positive metaphases (Ph+) was determined by conventional metaphase analysis. To confirm the prognostic significance of early molecular response, an independent validation sample of 174 pts treated with imatinib within the IRIS trial was analyzed. Results: The persistence of 〉 10% BCR-ABL IS at 3 months separated a high-risk group (28% of pts; 5-year OS: 87%) from a group with 1-10% BCR-ABL IS (41% of pts; 5-year OS: 94%; p=0.012), and from a group with 〈 1% BCR-ABL IS (31% of pts; 5-year OS: 97%; p=0.004). By cytogenetics high-risk patients could be identified by the persistence of 〉 35% Ph+ (27% of pts; 5-year OS: 87%) as compared to ≤35% Ph+ (73% of pts; 5-year OS: 95%; p=0.036). At 6 months the 〉 1% BCR-ABL IS group (37% of pts; 5-year OS: 89%) showed inferior survival compared to ≤1% (63% of pts; 5-year OS: 97%; p 〈 0.001); survival of the 〉 0% Ph+ group (34% of pts; 5-year OS: 91%) was inferior to 0% Ph+ (66% of pts; 5-year OS: 97%; p=0.015). Regarding the IRIS pts 3 month BCR-ABL IS 〉 10% (25% of pts; 8-year OS: 81%) was associated with inferior survival compared to ≤10% (75% of pts; 8-year OS: 93%; p=0.011). Conclusions: Failure to achieve the response landmarks of 10% BCR-ABL IS or 35% Ph+ at 3 months of imatinib treatment and 1% BCR-ABL IS or 0% Ph+ at 6 months identifies high-risk patients which might benefit from an early change of therapy.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2012.30.15_suppl.6510
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
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    Online Resource
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