دورية أكاديمية
Exploring Predictors of Response to Dacomitinib in EGFR -Amplified Recurrent Glioblastoma.
| العنوان: | Exploring Predictors of Response to Dacomitinib in EGFR -Amplified Recurrent Glioblastoma. |
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| المؤلفون: | Chi AS; Massachusetts General Hospital and Harvard Medical School, Boston, MA., Cahill DP; Massachusetts General Hospital and Harvard Medical School, Boston, MA., Reardon DA; Dana-Farber/Brigham and Women's Cancer Center and Harvard Medical School, Boston, MA., Wen PY; Dana-Farber/Brigham and Women's Cancer Center and Harvard Medical School, Boston, MA., Mikkelsen T; Ontario Brain Institute, Toronto, Ontario, Canada.; Henry Ford Hospital, Detroit, MI., Peereboom DM; Cleveland Clinic, Cleveland, OH., Wong ET; Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA., Gerstner ER; Massachusetts General Hospital and Harvard Medical School, Boston, MA., Dietrich J; Massachusetts General Hospital and Harvard Medical School, Boston, MA., Plotkin SR; Massachusetts General Hospital and Harvard Medical School, Boston, MA., Norden AD; Dana-Farber/Brigham and Women's Cancer Center and Harvard Medical School, Boston, MA., Lee EQ; Dana-Farber/Brigham and Women's Cancer Center and Harvard Medical School, Boston, MA., Nayak L; Dana-Farber/Brigham and Women's Cancer Center and Harvard Medical School, Boston, MA., Tanaka S; Massachusetts General Hospital and Harvard Medical School, Boston, MA., Wakimoto H; Massachusetts General Hospital and Harvard Medical School, Boston, MA., Lelic N; Massachusetts General Hospital and Harvard Medical School, Boston, MA., Koerner MV; Massachusetts General Hospital and Harvard Medical School, Boston, MA., Klofas LK; Massachusetts General Hospital and Harvard Medical School, Boston, MA., Bertalan MS; Massachusetts General Hospital and Harvard Medical School, Boston, MA., Arrillaga-Romany IC; Massachusetts General Hospital and Harvard Medical School, Boston, MA., Betensky RA; Harvard School of Public Health, Boston, MA., Curry WT; Massachusetts General Hospital and Harvard Medical School, Boston, MA., Borger DR; Massachusetts General Hospital and Harvard Medical School, Boston, MA., Balaj L; Massachusetts General Hospital and Harvard Medical School, Boston, MA., Kitchen RR; Exosome Diagnostics, Waltham, MA., Chakrabortty SK; Exosome Diagnostics, Waltham, MA., Valentino MD; Exosome Diagnostics, Waltham, MA., Skog J; Exosome Diagnostics, Waltham, MA., Breakefield XO; Massachusetts General Hospital and Harvard Medical School, Boston, MA., Iafrate AJ; Massachusetts General Hospital and Harvard Medical School, Boston, MA., Batchelor TT; Massachusetts General Hospital and Harvard Medical School, Boston, MA. |
| المصدر: | JCO precision oncology [JCO Precis Oncol] 2020 Jun 08; Vol. 4. Date of Electronic Publication: 2020 Jun 08 (Print Publication: 2020). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society of Clinical Oncology Country of Publication: United States NLM ID: 101705370 Publication Model: eCollection Cited Medium: Internet ISSN: 2473-4284 (Electronic) Linking ISSN: 24734284 NLM ISO Abbreviation: JCO Precis Oncol Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Alexandria, VA : American Society of Clinical Oncology, [2017]- |
| مستخلص: | Purpose: Despite the high frequency of EGFR genetic alterations in glioblastoma (GBM), EGFR-targeted therapies have not had success in this disease. To improve the likelihood of efficacy, we targeted adult patients with recurrent GBM enriched for EGFR gene amplification, which occurs in approximately half of GBM, with dacomitinib, a second-generation, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that penetrates the blood-brain barrier, in a multicenter phase II trial. Patients and Methods: We retrospectively explored whether previously described EGFR extracellular domain (ECD)-sensitizing mutations in the context of EGFR gene amplification could predict response to dacomitinib, and in a predefined subset of patients, we measured post-treatment intratumoral dacomitinib levels to verify tumor penetration. Results: We found that dacomitinib effectively penetrates contrast-enhancing GBM tumors. Among all 56 treated patients, 8 (14.3%) had a clinical benefit as defined by a duration of treatment of at least 6 months, of whom 5 (8.9%) remained progression free for at least 1 year. Presence of EGFRvIII or EGFR ECD missense mutation was not associated with clinical benefit. We evaluated the pretreatment transcriptome in circulating extracellular vesicles (EVs) by RNA sequencing in a subset of patients and identified a signature that distinguished patients who had durable benefit versus those with rapid progression. Conclusion: While dacomitinib was not effective in most patients with EGFR -amplified GBM, a subset experienced a durable, clinically meaningful benefit. Moreover, EGFRvIII and EGFR ECD mutation status in archival tumors did not predict clinical benefit. RNA signatures in circulating EVs may warrant investigation as biomarkers of dacomitinib efficacy in GBM. Competing Interests: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments). Andrew S. ChiEmployment: Neon Therapeutics, Mirati Therapeutics Consulting or Advisory Role: Cota Healthcare Patents, Royalties, Other Intellectual Property: Fused Bicyclic Heterocycles as Therapeutic Agents (inventor) provisional patent application No. 62/742,041 filed on October 5, 2018 Travel, Accommodations, Expenses: AbbVieDaniel P. CahillHonoraria: Merck Consulting or Advisory Role: Eli Lilly Travel, Accommodations, Expenses: MerckDavid A. ReardonHonoraria: Merck, Novartis, Novocure, Regeneron Pharmaceuticals, Bristol-Myers Squibb, Oncorus, Agenus, EMD Serono, Merck KGaA, Taiho Pharmaceutical, Advantagene, Bayer AG, Delmar Pharmaceuticals, Imvax Consulting or Advisory Role: Merck, Novartis, Novocure, Regeneron Pharmaceuticals, Bristol-Myers Squibb, Oncorus, Agenus, EMD Serono, Merck KGaA, Taiho Pharmaceutical, Delmar Pharmaceuticals, Advantagene, Bayer AG, Imvax Research Funding: Celldex (Inst), Incyte (Inst), Agenus (Inst), EMD Serono (Inst), Acerta Pharma (Inst), Omniox (Inst)Patrick Y. WenConsulting or Advisory Role: Agios, AstraZeneca, Vascular Biogenics, Immunomic Therapeutics, Kayatec, Puma Biotechnology, Taiho Pharmaceutical, Deciphera, VBI Vaccines, Tocagen, Bayer AG, Blue Earth Diagnostics, Karyopharm, Deciphera, Voyager, Taiho Pharmaceutical, QED, Imvax, Elevate Bio, Integral Health Speakers’ Bureau: Merck, Prime Oncology Research Funding: Agios (Inst), AbbVie (Inst), AstraZeneca (Inst), Merck (Inst), Novartis (Inst), Oncoceutics (Inst), Eli Lilly (Inst), AstraZeneca (Inst), BeiGene (Inst), Kazia (Inst), MediciNova (Inst), Vacular Biogenics (Inst), VBI Vaccines (Inst), Puma Biotechnology (Inst), Celgene (Inst), Bayer AG (Inst)Tom MikkelsenHonoraria: Roche, Genentech Travel, Accommodations, Expenses: Roche, GenentechDavid M. PeereboomConsulting or Advisory Role: Orbus Therapeutics Research Funding: Stemline Therapeutics (Inst), Pfizer (Inst), Novartis (Inst), Neonc Technologies (Inst), Orbus Therapeutics (Inst), Bristol-Myers Squibb (Inst), Genentech (Inst), Roche (Inst), Mylan (Inst) Travel, Accommodations, Expenses: Stemline TherapeuticsEric T. WongHonoraria: Novocure, UpToDate, Advanced Medical, ZaiLab Consulting or Advisory Role: Turning Point Therapeutics Research Funding: Novocure, Orbus, Vascular Biogenics, Five Prime Therapeutics, PlexxikonElizabeth R. GerstnerConsulting or Advisory Role: Blue Earth Diagnostics, MyoKardia (I), Array BioPharma (I)Jorg DietrichHonoraria: Unum Therapeutics, Blue Earth Diagnostics Consulting or Advisory Role: Blue Earth Diagnostics Patents, Royalties, Other Intellectual Property: UpToDateScott R. PlotkinStock and Other Ownership Interests: NFlection Therapeutics, NF2 Therapeutics Consulting or Advisory Role: AstraZeneca, NFlection Therapeutics Research Funding: Takeda Pharmaceuticals (Inst) Travel, Accommodations, Expenses: NFlection Therapeutics Uncompensated Relationships: Pfizer (Inst)Andrew D. NordenEmployment: Cota Healthcare, Oncology Analytics Leadership: Cota Healthcare, Oncology Analytics Stock and Other Ownership Interests: Cota Healthcare, Oncology AnalyticsEudocia Q. LeeHonoraria: Medlink Consulting or Advisory Role: Eli Lilly, Prime Oncology Patents, Royalties, Other Intellectual Property: Royalties from Wolters Kluwer for Up to DateLakshmi NayakTravel, Accommodations, Expenses: Bristol-Myers SquibbShota TanakaResearch Funding: Ono Pharmaceutical, Sumitomo Dainippon, Eisai Patents, Royalties, Other Intellectual Property: P2019-095102Mara V. KoernerEmployment: Cygnal Therapeutics, Ultivue Stock and Other Ownership Interests: Cygnal Therapeutics, Ultivue Research Funding: Cygnal Therapeutics, UltivueIsabel C. Arrillaga-RomanyHonoraria: Merck Consulting or Advisory Role: Insys Therapeutics, Karus Therapeutics, Agios, Boehringer Ingelheim, FORMA Therapeutics Research Funding: Astex PharmaceuticalsRebecca A. BetenskyConsulting or Advisory Role: Biogen, Reata, Alexion Pharmaceuticals, Quark, Intracellular Therapies Expert Testimony: TEVA Pharmaceuticals Industries, AmarinDarrel R. BorgerEmployment: Takeda Pharmaceuticals Stock and Other Ownership Interests: Takeda PharmaceuticalsLeonora BalajEmployment: Exosome Diagnostics (I) Leadership: Exosome Diagnostics (I) Stock and Other Ownership Interests: Exosome Diagnostics (I) Patents, Royalties, Other Intellectual Property: Massachusetts General Hospital (MGH) has intellectual property on exosome cancer diagnostics and inventor and receives royalties (I); co-inventor and receive royalties from MGH; many patents through Exosome Diagnostics (I)Robert R. KitchenEmployment: Exosome Diagnostics Stock and Other Ownership Interests: Exosome Diagnostics Patents, Royalties, Other Intellectual Property: Several patents pending for inventions while employed at Exosome DiagnosticsSudipto K. ChakraborttyEmployment: Exosome Diagnostics Stock and Other Ownership Interests: Exosome Diagnostics Research Funding: Exosome Diagnostics Patents, Royalties, Other Intellectual Property: Patents pending for work at Exosome Diagnostics Travel, Accommodations, Expenses: Exosome DiagnosticsMichael D. ValentinoEmployment: Exosome Diagnostics Stock and Other Ownership Interests: Exosome Diagnostics Research Funding: Exosome Diagnostics Patents, Royalties, Other Intellectual Property: RNA-seq patents as co-discoverer while working at Exosome Diagnostics Travel, Accommodations, Expenses: Exosome DiagnosticsA. John IafrateStock and Other Ownership Interests: Archer Biosciences Consulting or Advisory Role: Debiopharm Group, Chugai Pharma, Roche, Repare Therapeutics, Research Funding: Sanofi Patents, Royalties, Other Intellectual Property: ArcherDx exclusive license to AMP technologyTracy T. BatchelorHonoraria: UpToDate Consulting or Advisory Role: GenomiCare, Amgen Travel, Accommodations, Expenses: GenomiCare No other potential conflicts of interest were reported. (© 2020 by American Society of Clinical Oncology.) |
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| معلومات مُعتمدة: | P01 CA069246 United States CA NCI NIH HHS; R35 CA232103 United States CA NCI NIH HHS |
| تواريخ الأحداث: | Date Created: 20200914 Latest Revision: 20210615 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC7446412 |
| DOI: | 10.1200/PO.19.00295 |
| PMID: | 32923886 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2473-4284 |
|---|---|
| DOI: | 10.1200/PO.19.00295 |