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Melanoma: HELP
Articles by Michael D. Pickard
Based on 3 articles published since 2008
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Between 2008 and 2019, Michael D. Pickard wrote the following 3 articles about Melanoma.
 
+ Citations + Abstracts
1 Clinical Trial Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial. 2018

Dummer, Reinhard / Ascierto, Paolo A / Gogas, Helen J / Arance, Ana / Mandala, Mario / Liszkay, Gabriella / Garbe, Claus / Schadendorf, Dirk / Krajsova, Ivana / Gutzmer, Ralf / Chiarion-Sileni, Vanna / Dutriaux, Caroline / de Groot, Jan Willem B / Yamazaki, Naoya / Loquai, Carmen / Moutouh-de Parseval, Laure A / Pickard, Michael D / Sandor, Victor / Robert, Caroline / Flaherty, Keith T. ·Department of Dermatology, University Hospital Zürich Skin Cancer Center, Zürich, Switzerland. Electronic address: reinhard.dummer@usz.ch. · Melanoma Unit, Cancer Immunotherapy and Innovative Therapies, Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy. · Department of Internal Medicine, National and Kapodistrian University of Athens, Laikon Hospital, Athens, Greece. · Department of Medical Oncology, Hospital Clinic of Barcelona, Barcelona, Spain. · Department of Oncology and Haematology, Papa Giovanni XXIII Cancer Center Hospital, Bergamo, Italy. · Department of Dermatology, National Institute of Oncology, Budapest, Hungary. · Department of Dermatology, University Hospital Tüebingen, Tüebingen, Germany. · Department of Dermatology, University Hospital Essen, Essen, Germany; German Cancer Consortium, Heidelberg, Germany. · Department of Dermato-oncology, University Hospital Prague, Charles University First Medical Faculty, Prague, Czech Republic. · Department of Dermatology and Allergy, Skin Cancer Center Hannover, Hannover Medical School, Hannover, Germany. · Melanoma Cancer Unit, Oncology Institute of Veneto IRCCS, Padua, Italy. · Department of Oncologic Dermatology, Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux, France. · Department of Medical Oncology, Isala, Zwolle, Netherlands. · Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, Japan. · Department of Dermatology, University Medical Center Mainz, Mainz, Germany. · Translational Clinical Oncology, Novartis Pharma AG, Basel, Switzerland. · Array BioPharma, Boulder, CO, USA. · Service of Dermatology, Department of Medicine, Paris-Sud University, Gustave Roussy, Villejuif, France. · Cancer Center, Massachusetts General Hospital, Boston, MA, USA. ·Lancet Oncol · Pubmed #29573941.

ABSTRACT: BACKGROUND: Combined BRAF-MEK inhibitor therapy is the standard of care for BRAF METHODS: COLUMBUS was conducted as a two-part, randomised, open-label phase 3 study at 162 hospitals in 28 countries. Eligible patients were aged 18 years or older and had histologically confirmed locally advanced (American Joint Committee on Cancer [AJCC] stage IIIB, IIIC, or IV), unresectable or metastatic cutaneous melanoma, or unknown primary melanoma; a BRAF FINDINGS: Between Dec 30, 2013, and April 10, 2015, 577 of 1345 screened patients were randomly assigned to either the encorafenib plus binimetinib group (n=192), the encorafenib group (n=194), or the vemurafenib group (n=191). With a median follow-up of 16·6 months (95% CI 14·8-16·9), median progression-free survival was 14·9 months (95% CI 11·0-18·5) in the encorafenib plus binimetinib group and 7·3 months (5·6-8·2) in the vemurafenib group (hazard ratio [HR] 0·54, 95% CI 0·41-0·71; two-sided p<0·0001). The most common grade 3-4 adverse events seen in more than 5% of patients in the encorafenib plus binimetinib group were increased γ-glutamyltransferase (18 [9%] of 192 patients), increased creatine phosphokinase (13 [7%]), and hypertension (11 [6%]); in the encorafenib group they were palmoplantar erythrodysaesthesia syndrome (26 [14%] of 192 patients), myalgia (19 [10%]), and arthralgia (18 [9%]); and in the vemurafenib group it was arthralgia (11 [6%] of 186 patients). There were no treatment-related deaths except for one death in the combination group, which was considered possibly related to treatment by the investigator. INTERPRETATION: Encorafenib plus binimetinib and encorafenib monotherapy showed favourable efficacy compared with vemurafenib. Overall, encorafenib plus binimetinib appears to have an improved tolerability profile compared with encorafenib or vemurafenib. Encorafenib plus binimetinib could represent a new treatment option for patients with BRAF-mutant melanoma. FUNDING: Array BioPharma, Novartis.

2 Clinical Trial A phase I study of the investigational NEDD8-activating enzyme inhibitor pevonedistat (TAK-924/MLN4924) in patients with metastatic melanoma. 2016

Bhatia, Shailender / Pavlick, Anna C / Boasberg, Peter / Thompson, John A / Mulligan, George / Pickard, Michael D / Faessel, Hélène / Dezube, Bruce J / Hamid, Omid. ·Department of Medicine/Medical Oncology, University of Washington Medical Center/Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, 825 Eastlake Ave W, G4-830, Seattle, WA, 98109-1023, USA. sbhatia@uw.edu. · Departments of Medicine (Perlmutter Cancer Center) and Dermatology, NYU Langone Medical Center, New York, NY, USA. · The Angeles Clinic and Research Institute, Translational Research & Cutaneous Oncology, Los Angeles, CA, USA. · Department of Medicine/Medical Oncology, University of Washington Medical Center/Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, 825 Eastlake Ave W, G4-830, Seattle, WA, 98109-1023, USA. · Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA. ·Invest New Drugs · Pubmed #27056178.

ABSTRACT: Purpose The therapeutic index of proteasome inhibitors may be improved through selective inhibition of a sub-component of the ubiquitin-proteasome system, such as the NEDD8-conjugation pathway. This multicenter, phase I, dose-escalation study assessed safety and the maximum tolerated dose (MTD), pharmacokinetics, pharmacodynamics, and antitumor activity of pevonedistat, an investigational NEDD8-activating enzyme (NAE) inhibitor, in patients with metastatic melanoma. Methods Patients received intravenous pevonedistat on Days 1, 4, 8, 11 (schedule A) or 1, 8, 15 (schedule B) of 21-day cycles. Results 26 patients received pevonedistat 50-278 mg/m(2) on schedule A; 11 patients received pevonedistat 157 mg/m(2) on schedule B. The schedule A MTD was 209 mg/m(2): dose-limiting toxicities (DLTs) included grade 3 hypophosphatemia and grade 3 increased blood creatinine (associated with grade 3 hyperbilirubinemia). Two schedule A patients experienced acute organ failure toxicities, one of whom experienced grade 5 acute renal failure. Dose escalation did not occur in schedule B: DLTs included grade 3 myocarditis, grade 2 acute renal failure, and grade 2 hyperbilirubinemia in a single patient. Pevonedistat pharmacokinetics were approximately dose-proportional across the dose range studied, with a biphasic disposition profile characterized by a short elimination half-life (~10 h). Pharmacodynamic studies showed increases in NAE-regulated transcripts post-treatment; all post-dose biopsy samples were positive for pevonedistat-NEDD8 adduct. One schedule A patient achieved a partial response; 15 patients had stable disease (4 lasting ≥6.5 months). Conclusions Pevonedistat was generally well tolerated at the MTD. Anticipated pharmacodynamic effects of NAE inhibition were observed with single-agent pevonedistat in peripheral blood and tumor tissue.

3 Article Genome-wide siRNA screen for modulators of cell death induced by proteasome inhibitor bortezomib. 2010

Chen, Siquan / Blank, Jonathan L / Peters, Theodore / Liu, Xiaozhen J / Rappoli, David M / Pickard, Michael D / Menon, Saurabh / Yu, Jie / Driscoll, Denise L / Lingaraj, Trupti / Burkhardt, Anne L / Chen, Wei / Garcia, Khristofer / Sappal, Darshan S / Gray, Jesse / Hales, Paul / Leroy, Patrick J / Ringeling, John / Rabino, Claudia / Spelman, James J / Morgenstern, Jay P / Lightcap, Eric S. ·Discovery Technologies, Discovery Oncology Biology, and Medical Biostatistics, Millennium Pharmaceuticals, Inc., Cambridge, MA 02139, USA. ·Cancer Res · Pubmed #20460535.

ABSTRACT: Multiple pathways have been proposed to explain how proteasome inhibition induces cell death, but mechanisms remain unclear. To approach this issue, we performed a genome-wide siRNA screen to evaluate the genetic determinants that confer sensitivity to bortezomib (Velcade (R); PS-341). This screen identified 100 genes whose knockdown affected lethality to bortezomib and to a structurally diverse set of other proteasome inhibitors. A comparison of three cell lines revealed that 39 of 100 genes were commonly linked to cell death. We causally linked bortezomib-induced cell death to the accumulation of ASF1B, Myc, ODC1, Noxa, BNIP3, Gadd45alpha, p-SMC1A, SREBF1, and p53. Our results suggest that proteasome inhibition promotes cell death primarily by dysregulating Myc and polyamines, interfering with protein translation, and disrupting essential DNA damage repair pathways, leading to programmed cell death.