دورية أكاديمية
Effects of Molecular Heterogeneity on Survival of Patients With BRAF V600 -Mutated Melanoma Treated With Vemurafenib With or Without Cobimetinib in the coBRIM Study.
| العنوان: | Effects of Molecular Heterogeneity on Survival of Patients With BRAF V600 -Mutated Melanoma Treated With Vemurafenib With or Without Cobimetinib in the coBRIM Study. |
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| المؤلفون: | Wongchenko MJ; Matthew J. Wongchenko, Ilsung Chang, Jessie Hsu, Isabelle Rooney, William Lu, Hartmut Koeppen, and Yibing Yan, Genentech, South San Francisco; Antoni Ribas, Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, Los Angeles, CA; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples; Anna Maria di Giacomo, Azienda Ospedaliera Universitaria Senese, Siena, Italy; Brigitte Dréno, Nantes University, Nantes, France; Claus Garbe, University of Tübingen, Tübingen, Germany; James Larkin, The Royal Marsden Hospital, London, United Kingdom; Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; and Grant A. McArthur, University of Melbourne, Parkville, Victoria, Australia., Ribas A; Matthew J. Wongchenko, Ilsung Chang, Jessie Hsu, Isabelle Rooney, William Lu, Hartmut Koeppen, and Yibing Yan, Genentech, South San Francisco; Antoni Ribas, Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, Los Angeles, CA; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples; Anna Maria di Giacomo, Azienda Ospedaliera Universitaria Senese, Siena, Italy; Brigitte Dréno, Nantes University, Nantes, France; Claus Garbe, University of Tübingen, Tübingen, Germany; James Larkin, The Royal Marsden Hospital, London, United Kingdom; Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; and Grant A. McArthur, University of Melbourne, Parkville, Victoria, Australia., Ascierto PA; Matthew J. Wongchenko, Ilsung Chang, Jessie Hsu, Isabelle Rooney, William Lu, Hartmut Koeppen, and Yibing Yan, Genentech, South San Francisco; Antoni Ribas, Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, Los Angeles, CA; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples; Anna Maria di Giacomo, Azienda Ospedaliera Universitaria Senese, Siena, Italy; Brigitte Dréno, Nantes University, Nantes, France; Claus Garbe, University of Tübingen, Tübingen, Germany; James Larkin, The Royal Marsden Hospital, London, United Kingdom; Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; and Grant A. McArthur, University of Melbourne, Parkville, Victoria, Australia., Dréno B; Matthew J. Wongchenko, Ilsung Chang, Jessie Hsu, Isabelle Rooney, William Lu, Hartmut Koeppen, and Yibing Yan, Genentech, South San Francisco; Antoni Ribas, Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, Los Angeles, CA; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples; Anna Maria di Giacomo, Azienda Ospedaliera Universitaria Senese, Siena, Italy; Brigitte Dréno, Nantes University, Nantes, France; Claus Garbe, University of Tübingen, Tübingen, Germany; James Larkin, The Royal Marsden Hospital, London, United Kingdom; Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; and Grant A. McArthur, University of Melbourne, Parkville, Victoria, Australia., Maria di Giacomo A; Matthew J. Wongchenko, Ilsung Chang, Jessie Hsu, Isabelle Rooney, William Lu, Hartmut Koeppen, and Yibing Yan, Genentech, South San Francisco; Antoni Ribas, Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, Los Angeles, CA; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples; Anna Maria di Giacomo, Azienda Ospedaliera Universitaria Senese, Siena, Italy; Brigitte Dréno, Nantes University, Nantes, France; Claus Garbe, University of Tübingen, Tübingen, Germany; James Larkin, The Royal Marsden Hospital, London, United Kingdom; Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; and Grant A. McArthur, University of Melbourne, Parkville, Victoria, Australia., Garbe C; Matthew J. Wongchenko, Ilsung Chang, Jessie Hsu, Isabelle Rooney, William Lu, Hartmut Koeppen, and Yibing Yan, Genentech, South San Francisco; Antoni Ribas, Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, Los Angeles, CA; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples; Anna Maria di Giacomo, Azienda Ospedaliera Universitaria Senese, Siena, Italy; Brigitte Dréno, Nantes University, Nantes, France; Claus Garbe, University of Tübingen, Tübingen, Germany; James Larkin, The Royal Marsden Hospital, London, United Kingdom; Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; and Grant A. McArthur, University of Melbourne, Parkville, Victoria, Australia., Chang I; Matthew J. Wongchenko, Ilsung Chang, Jessie Hsu, Isabelle Rooney, William Lu, Hartmut Koeppen, and Yibing Yan, Genentech, South San Francisco; Antoni Ribas, Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, Los Angeles, CA; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples; Anna Maria di Giacomo, Azienda Ospedaliera Universitaria Senese, Siena, Italy; Brigitte Dréno, Nantes University, Nantes, France; Claus Garbe, University of Tübingen, Tübingen, Germany; James Larkin, The Royal Marsden Hospital, London, United Kingdom; Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; and Grant A. McArthur, University of Melbourne, Parkville, Victoria, Australia., Hsu J; Matthew J. Wongchenko, Ilsung Chang, Jessie Hsu, Isabelle Rooney, William Lu, Hartmut Koeppen, and Yibing Yan, Genentech, South San Francisco; Antoni Ribas, Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, Los Angeles, CA; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples; Anna Maria di Giacomo, Azienda Ospedaliera Universitaria Senese, Siena, Italy; Brigitte Dréno, Nantes University, Nantes, France; Claus Garbe, University of Tübingen, Tübingen, Germany; James Larkin, The Royal Marsden Hospital, London, United Kingdom; Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; and Grant A. McArthur, University of Melbourne, Parkville, Victoria, Australia., Rooney I; Matthew J. Wongchenko, Ilsung Chang, Jessie Hsu, Isabelle Rooney, William Lu, Hartmut Koeppen, and Yibing Yan, Genentech, South San Francisco; Antoni Ribas, Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, Los Angeles, CA; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples; Anna Maria di Giacomo, Azienda Ospedaliera Universitaria Senese, Siena, Italy; Brigitte Dréno, Nantes University, Nantes, France; Claus Garbe, University of Tübingen, Tübingen, Germany; James Larkin, The Royal Marsden Hospital, London, United Kingdom; Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; and Grant A. McArthur, University of Melbourne, Parkville, Victoria, Australia., Lu W; Matthew J. Wongchenko, Ilsung Chang, Jessie Hsu, Isabelle Rooney, William Lu, Hartmut Koeppen, and Yibing Yan, Genentech, South San Francisco; Antoni Ribas, Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, Los Angeles, CA; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples; Anna Maria di Giacomo, Azienda Ospedaliera Universitaria Senese, Siena, Italy; Brigitte Dréno, Nantes University, Nantes, France; Claus Garbe, University of Tübingen, Tübingen, Germany; James Larkin, The Royal Marsden Hospital, London, United Kingdom; Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; and Grant A. McArthur, University of Melbourne, Parkville, Victoria, Australia., Koeppen H; Matthew J. Wongchenko, Ilsung Chang, Jessie Hsu, Isabelle Rooney, William Lu, Hartmut Koeppen, and Yibing Yan, Genentech, South San Francisco; Antoni Ribas, Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, Los Angeles, CA; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples; Anna Maria di Giacomo, Azienda Ospedaliera Universitaria Senese, Siena, Italy; Brigitte Dréno, Nantes University, Nantes, France; Claus Garbe, University of Tübingen, Tübingen, Germany; James Larkin, The Royal Marsden Hospital, London, United Kingdom; Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; and Grant A. McArthur, University of Melbourne, Parkville, Victoria, Australia., Larkin J; Matthew J. Wongchenko, Ilsung Chang, Jessie Hsu, Isabelle Rooney, William Lu, Hartmut Koeppen, and Yibing Yan, Genentech, South San Francisco; Antoni Ribas, Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, Los Angeles, CA; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples; Anna Maria di Giacomo, Azienda Ospedaliera Universitaria Senese, Siena, Italy; Brigitte Dréno, Nantes University, Nantes, France; Claus Garbe, University of Tübingen, Tübingen, Germany; James Larkin, The Royal Marsden Hospital, London, United Kingdom; Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; and Grant A. McArthur, University of Melbourne, Parkville, Victoria, Australia., Yan Y; Matthew J. Wongchenko, Ilsung Chang, Jessie Hsu, Isabelle Rooney, William Lu, Hartmut Koeppen, and Yibing Yan, Genentech, South San Francisco; Antoni Ribas, Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, Los Angeles, CA; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples; Anna Maria di Giacomo, Azienda Ospedaliera Universitaria Senese, Siena, Italy; Brigitte Dréno, Nantes University, Nantes, France; Claus Garbe, University of Tübingen, Tübingen, Germany; James Larkin, The Royal Marsden Hospital, London, United Kingdom; Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; and Grant A. McArthur, University of Melbourne, Parkville, Victoria, Australia., McArthur GA; Matthew J. Wongchenko, Ilsung Chang, Jessie Hsu, Isabelle Rooney, William Lu, Hartmut Koeppen, and Yibing Yan, Genentech, South San Francisco; Antoni Ribas, Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, Los Angeles, CA; Paolo A. Ascierto, Istituto Nazionale Tumori Fondazione G. Pascale, Naples; Anna Maria di Giacomo, Azienda Ospedaliera Universitaria Senese, Siena, Italy; Brigitte Dréno, Nantes University, Nantes, France; Claus Garbe, University of Tübingen, Tübingen, Germany; James Larkin, The Royal Marsden Hospital, London, United Kingdom; Grant A. McArthur, Peter MacCallum Cancer Centre, East Melbourne; and Grant A. McArthur, University of Melbourne, Parkville, Victoria, Australia. |
| المصدر: | JCO precision oncology [JCO Precis Oncol] 2018 Nov; Vol. 2, pp. 1-18. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society of Clinical Oncology Country of Publication: United States NLM ID: 101705370 Publication Model: Print Cited Medium: Internet ISSN: 2473-4284 (Electronic) Linking ISSN: 24734284 NLM ISO Abbreviation: JCO Precis Oncol Subsets: PubMed not MEDLINE; MEDLINE |
| أسماء مطبوعة: | Original Publication: Alexandria, VA : American Society of Clinical Oncology, [2017]- |
| مستخلص: | Purpose: The treatment of advanced BRAF V600 -mutated melanomas with BRAF inhibitors (BRAFi) has improved survival, but the efficacy of BRAFi varies among individuals and the development of acquired resistance to BRAFi through reactivation of mitogen-activated protein kinase (MAPK) signaling is common. We performed an exploratory, retrospective analysis to investigate the effects of BRAF V600 allelic balance, coexisting oncogene mutations, cell proliferation signaling levels, and loss of PTEN expression on progression-free survival (PFS) in patients in the phase III coBRIM study, which compared the combination of the MEK inhibitor cobimetinib with the BRAFi vemurafenib versus vemurafenib as monotherapy. Methods: Baseline tumor samples from the intention-to-treat population were analyzed by targeted deep sequencing at a median coverage of 3,600× and by immunohistochemistry for cell proliferation markers, BRAF V600E , and PTEN. The association of these biomarkers with PFS was assessed by Cox proportional hazards modeling. Gene expression in relation to loss of PTEN was profiled by RNA sequencing in 205 patient samples and 42 BRAF V600 -mutated melanoma cell lines. Results: Neither BRAF V600 allelic balance nor coexisting mutations in the RAS/RAF/RTK pathway affected PFS in either treatment group. Increased baseline MAPK signaling and cell proliferation did not affect PFS in patients treated with cobimetinib combined with vemurafenib. PTEN loss was associated with reduced PFS in patients treated with vemurafenib alone but not in patients treated with cobimetinib combined with vemurafenib. Conclusion: Deeper inhibition of the MAPK pathway through targeting of both MEK and BRAF may override the effects of tumor heterogeneity and improve PFS in all patients with advanced BRAF V600 melanoma. |
| تواريخ الأحداث: | Date Created: 20220209 Latest Revision: 20220209 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1200/PO.17.00242 |
| PMID: | 35135126 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2473-4284 |
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| DOI: | 10.1200/PO.17.00242 |