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Melanoma: HELP
Articles by Matthew J. Wheater
Based on 8 articles published since 2010
(Why 8 articles?)
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Between 2010 and 2020, M. Wheater wrote the following 8 articles about Melanoma.
 
+ Citations + Abstracts
1 Article Paclitaxel with or without trametinib or pazopanib in advanced wild-type BRAF melanoma (PACMEL): a multicentre, open-label, randomised, controlled phase II trial. 2019

Urbonas, V / Schadendorf, D / Zimmer, L / Danson, S / Marshall, E / Corrie, P / Wheater, M / Plummer, E / Mauch, C / Scudder, C / Goff, M / Love, S B / Mohammed, S B / Middleton, M R. ·Early Phase Clinical Trials Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; National Cancer Institute, Vilnius, Lithuania. · Department of Dermatology, University Hospital Essen, West German Cancer Centre, University Duisburg-Essen, Essen, Germany; The German Cancer Consortium, Essen, Germany. · Department of Oncology, Sheffield Experimental Cancer Medicine Centre, Weston Park Hospital, Sheffield, UK. · Department of Oncology, Clatterbridge Cancer Centre, Wirral, UK. · Department of Oncology, Addenbrookes Hospital, Cambridge, UK. · Department of Oncology, Southampton General Hospital, Southampton, UK. · Department of Oncology, Freeman Hospital, Newcastle upon Tyne, UK. · Köln Universitätsklinik, Köln, Germany. · Oncology Clinical Trials Office, University of Oxford, Oxford, UK. · Centre for Statistics in Medicine, University of Oxford, Oxford, UK. · Early Phase Clinical Trials Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK; Department of Oncology, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK. Electronic address: mark.middleton@oncology.ox.ac.uk. ·Ann Oncol · Pubmed #31987431.

ABSTRACT: BACKGROUND: Advanced melanoma treatments often rely on immunotherapy or targeting mutations, with few treatment options for wild-type BRAF (BRAF-wt) melanoma. However, the mitogen-activated protein kinase pathway is activated in most melanoma, including BRAF-wt. We assessed whether inhibiting this pathway by adding kinase inhibitors trametinib or pazopanib to paclitaxel chemotherapy improved outcomes in patients with advanced BRAF-wt melanoma in a phase II, randomised and open-label trial. PATIENTS AND METHODS: Patients were randomised (1 : 1 : 1) to paclitaxel alone or with trametinib or pazopanib. Paclitaxel was given for a maximum of six cycles, while 2 mg trametinib and 800 mg pazopanib were administered orally once daily until disease progression or unacceptable toxicity. Participants and investigators were unblinded. The primary end point was progression-free survival (PFS). Key secondary end points included overall survival (OS) and objective response rate (ORR). RESULTS: Participants were randomised to paclitaxel alone (n = 38), paclitaxel and trametinib (n = 36), or paclitaxel and pazopanib (n = 37). Adding trametinib significantly improved 6-month PFS [time ratio (TR), 1.47; 90% confidence interval (CI) 1.08-2.01, P = 0.04] and ORR (42% versus 13%; P = 0.01) but had no effect on OS (P = 0.25). Adding pazopanib did not benefit 6-month PFS; (TR 1.36; 90% CI 0.96-1.93; P = 0.14), ORR, or OS. Toxicity increased in both combination arms. CONCLUSION: In this phase II trial, adding trametinib to paclitaxel chemotherapy for BRAF-wt melanoma improved PFS and substantially increased ORR but did not impact OS. This study was registered with the EU Clinical Trials Register, EudraCT number 2011-002545-35, and with the ISRCTN registry, number 43327231.

2 Article Paclitaxel with or without trametinib or pazopanib in advanced wild-type BRAF melanoma (PACMEL): a multicentre, open-label, randomised, controlled phase II trial. 2019

Urbonas, V / Schadendorf, D / Zimmer, L / Danson, S / Marshall, E / Corrie, P / Wheater, M / Plummer, E / Mauch, C / Scudder, C / Goff, M / Love, S B / Mohammed, S B / Middleton, M R. ·Early Phase Clinical Trials Unit, Oxford University Hospitals NHS Foundation Trust, Oxford, UK. · National Cancer Institute, Vilnius, Lithuania. · Department of Dermatology, University Hospital Essen, West German Cancer Centre, University Duisburg-Essen, Essen, Germany. · The German Cancer Consortium, Essen, Germany. · Department of Oncology, Sheffield Experimental Cancer Medicine Centre, Weston Park Hospital, Sheffield, UK. · Department of Oncology, Clatterbridge Cancer Centre, Wirral, UK. · Department of Oncology, Addenbrookes Hospital, Cambridge, UK. · Department of Oncology, Southampton General Hospital, Southampton, UK. · Department of Oncology, Freeman Hospital, Newcastle upon Tyne, UK. · Köln Universitätsklinik, Köln, Germany. · Oncology Clinical Trials Office, University of Oxford, Oxford, UK. · Centre for Statistics in Medicine, University of Oxford, Oxford, UK. · Department of Oncology, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK. ·Ann Oncol · Pubmed #30428063.

ABSTRACT: BACKGROUND: Advanced melanoma treatments often rely on immunotherapy or targeting mutations, with few treatment options for wild-type BRAF (BRAF-wt) melanoma. However, the mitogen-activated protein kinase pathway is activated in most melanoma, including BRAF-wt. We assessed whether inhibiting this pathway by adding kinase inhibitors trametinib or pazopanib to paclitaxel chemotherapy improved outcomes in patients with advanced BRAF-wt melanoma in a phase II, randomised and open-label trial. PATIENTS AND METHODS: Patients were randomised (1 : 1 : 1) to paclitaxel alone or with trametinib or pazopanib. Paclitaxel was given for a maximum of six cycles, while 2 mg trametinib and 800 mg pazopanib were administered orally once daily until disease progression or unacceptable toxicity. Participants and investigators were unblinded. The primary end point was progression-free survival (PFS). Key secondary end points included overall survival (OS) and objective response rate (ORR). RESULTS: Participants were randomised to paclitaxel alone (n = 38), paclitaxel and trametinib (n = 36), or paclitaxel and pazopanib (n = 37). Adding trametinib significantly improved 6-month PFS [time ratio (TR), 1.47; 90% confidence interval (CI) 1.08-2.01, P = 0.04] and ORR (42% versus 13%; P = 0.01) but had no effect on OS (P = 0.25). Adding pazopanib did not benefit 6-month PFS; (TR 1.36; 90% CI 0.96-1.93; P = 0.14), ORR, or OS. Toxicity increased in both combination arms. CONCLUSION: In this phase II trial, adding trametinib to paclitaxel chemotherapy for BRAF-wt melanoma improved PFS and substantially increased ORR but did not impact OS.This study was registered with the EU Clinical Trials Register, EudraCT number 2011-002545-35, and with the ISRCTN registry, number 43327231.

3 Article Percutaneous hepatic perfusion with melphalan in uveal melanoma: A safe and effective treatment modality in an orphan disease. 2018

Karydis, Ioannis / Gangi, Alexandra / Wheater, Matthew J / Choi, Junsung / Wilson, Iain / Thomas, Kerry / Pearce, Neil / Takhar, Arjun / Gupta, Sanjay / Hardman, Danielle / Sileno, Sean / Stedman, Brian / Zager, Jonathan S / Ottensmeier, Christian. ·Cancer Sciences Academic Unit, University of Southampton, Southampton, United Kingdom. · University Hospital Southampton, Southampton, United Kingdom. · Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, Florida. · Department of Radiology, Moffitt Cancer Center, Tampa, Florida. · Morsani School of Medicine, University of South Florida, Tampa, Florida. ·J Surg Oncol · Pubmed #29284076.

ABSTRACT: BACKGROUND: Metastatic uveal melanoma (UM) carries a poor prognosis; liver is the most frequent and often solitary site of recurrence. Available systemic treatments have not improved outcomes. Melphalan percutaneous hepatic perfusion (M-PHP) allows selective intrahepatic delivery of high dose cytotoxic chemotherapy. METHODS: Retrospective analysis of outcomes data of UM patients receiving M-PHP at two institutions was performed. Tumor response and toxicity were evaluated using RECIST 1.1 and Common Terminology Criteria for Adverse Events (CTCAE) v4.03, respectively. RESULTS: A total of 51 patients received 134 M-PHP procedures (median of 2 M-PHPs). 25 (49%) achieved a partial (N = 22, 43.1%) or complete hepatic response (N = 3, 5.9%). In 17 (33.3%) additional patients, the disease stabilized for at least 3 months, for a hepatic disease control rate of 82.4%. After median follow-up of 367 days, median overall progression free (PFS) and hepatic progression free survival (hPFS) was 8.1 and 9.1 months, respectively and median overall survival was 15.3 months. There were no treatment related fatalities. Non-hematologic grade 3-4 events were seen in 19 (37.5%) patients and were mainly coagulopathic (N = 8) and cardiovascular (N = 9). CONCLUSIONS: M-PHP results in durable intrahepatic disease control and can form the basis for an integrated multimodality treatment approach in appropriately selected UM patients.

4 Article Evaluation of immune infiltration in the colonic mucosa of patients with ipilimumab-related colitis. 2016

Arriola, Edurne / Wheater, Matthew / Lopez, Maria Antonette / Thomas, Gareth / Ottensmeier, Christian. ·Southampton NIHR Experimental Cancer Medicine Center, Faculty of Medicine, University of Southampton, Southampton, UK; University Hospital Southampton NHS Foundation Trust, Southampton, UK. · University Hospital Southampton NHS Foundation Trust , Southampton, UK. ·Oncoimmunology · Pubmed #27757302.

ABSTRACT: Approximately 30% of patients treated with ipilimumab will develop gastrointestinal toxicity. The immunological drivers that underpin the clinical observations in human tissues are poorly understood. We report here on the immune consequences of ipilimumab treatment in the colorectal mucosa of patients with treatment-related colitis. Using immunohistochemistry, we evaluated the immune infiltrate by CD8

5 Article Clinical activity and safety of Pembrolizumab in Ipilimumab pre-treated patients with uveal melanoma. 2016

Karydis, Ioannis / Chan, Pui Ying / Wheater, Matthew / Arriola, Edurne / Szlosarek, Peter W / Ottensmeier, Christian H. ·Cancer Sciences Academic Unit, University of Southampton , Southampton, United Kingdom. · Department of Medical Oncology, St Bartholomew's Hospital , London. · Medical Oncology, University Hospital Southampton , Southampton, United Kingdom. · Department of Medical Oncology, St Bartholomew's Hospital, London; Barts Cancer Institute, Queen Mary University of London, London. ·Oncoimmunology · Pubmed #27467964.

ABSTRACT: BACKGROUND: Untreated metastatic uveal melanoma (UM) carries a grave prognosis. Unlike cutaneous melanoma (CM), there are no established treatments known to significantly improve outcomes for a meaningful proportion of patients. Inhibition of the PD1-PDL1 axis has shown promise in the management of CM and we here report a two center experience of UM patients receiving pembrolizumab. METHODS: To assess the efficacy and safety of pembrolizumab, we retrospectively analyzed outcome data of 25 consecutive UM patients participating in the MK3475 expanded access program (EAP) who received pembrolizumab at 2 mg/kg 3 weekly. Tumor assessment was evaluated using RECIST 1.1 and immune-related Response Criteria (irRC) by CT scanning. Toxicity was recorded utilizing Common Terminology Criteria for Adverse Events ("CTCAE") v4.03. RESULTS: Twenty-five patients were identified receiving a median of six cycles of treatment. Two patients achieved a partial response and six patients stable disease. After a median follow-up of 225 d median progression free survival (PFS) was 91 d and overall survival (OS) was not reached. There was a significant trend for improved outcomes in patients with extrahepatic disease progression as opposed to liver only progression at the outset. Five patients experienced grade 3 or 4 adverse events (AEs); there were no treatment related deaths. CONCLUSIONS: Pembrolizumab 2mg/kg q3w is a safe option in UM patients. Disease control rates, particularly in the subgroup of patients without progressive liver disease at the outset are promising; these results merit further investigation in clinical trials possibly incorporating liver targeted treatment modalities.

6 Article Immunosuppression for ipilimumab-related toxicity can cause 2015

Arriola, Edurne / Wheater, Matthew / Krishnan, Radhika / Smart, James / Foria, Vipul / Ottensmeier, Christian. ·Cancer Sciences Unit; University of Southampton and University Hospital Southampton NHS Foundation Trust ; Southampton, UK ; University Hospital Southampton NHS Foundation Trust ; Southampton, UK ; Southampton Experimental Cancer Medicine Center; University of Southampton and University Hospital Southampton NHS Foundation Trust ; Southampton, UK. · University Hospital Southampton NHS Foundation Trust ; Southampton, UK ; Southampton Experimental Cancer Medicine Center; University of Southampton and University Hospital Southampton NHS Foundation Trust ; Southampton, UK. · University Hospital Southampton NHS Foundation Trust ; Southampton, UK. ·Oncoimmunology · Pubmed #26451305.

ABSTRACT: Ipilimumab is a standard therapy for advanced melanoma. Severe immune related adverse events occur in up to 30% of patients and require treatment with immunosuppressants such as steroids or the anti-TNFα antibody, infliximab. We describe two patients with advanced melanoma treated with ipilimumab. Both suffered from severe immune related side effects and required prolonged immunosuppression with steroids and/or infliximab. Both patients recovered and in spite of the immune suppression, demonstrate clinical evidence of tumor control. This argues that distinct immunological effector functions control nosocomial infection and tumor, respectively. To our knowledge, these are also the first two case reports of pneumocystis pneumonia in this setting.

7 Article Ipilimumab in the real world: the UK expanded access programme experience in previously treated advanced melanoma patients. 2015

Ahmad, Saif S / Qian, Wendi / Ellis, Sarah / Mason, Elaine / Khattak, Muhammad A / Gupta, Avinash / Shaw, Heather / Quinton, Amy / Kovarikova, Jarmila / Thillai, Kiruthikah / Rao, Ankit / Board, Ruth / Nobes, Jenny / Dalgleish, Angus / Grumett, Simon / Maraveyas, Anthony / Danson, Sarah / Talbot, Toby / Harries, Mark / Marples, Maria / Plummer, Ruth / Kumar, Satish / Nathan, Paul / Middleton, Mark R / Larkin, James / Lorigan, Paul / Wheater, Matthew / Ottensmeier, Christian H / Corrie, Pippa G. ·aDepartment of Oncology bCambridge Cancer Trials Centre, Cambridge Clinical Trials Unit - Cancer Theme, Cambridge University Hospitals NHS Foundation Trust, Cambridge cSouthampton Experimental Cancer Medicine Center, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton dDepartment of Medical Oncology, The Christie, Manchester eDepartment of Medicine, Royal Marsden NHS Foundation Trust, London fOxford NIHR Biomedical Research Centre, Oxford gDepartment of Medical Oncology, Mount Vernon Hospital, Northwood hDepartment of Medical Oncology, Velindre Cancer Centre, Cardiff iNorthern Centre for Cancer Care, Newcastle upon Tyne jDirectorate of Haematology and Oncology, Guy's and St. Thomas' NHS Foundation Trust, London kDepartment of Medical Oncology, Royal Wolverhampton Hospitals lDepartment of Medical Oncology, Royal Preston Hospital mClinical Oncology, Norfolk and Norwich University Hospital nDivision of Clinical Sciences, St George's Hospital Medical School, London oDepartment of Oncology, Castle Hill Hospital, Hull pSheffield Experimental Cancer Medicine Centre, University of Sheffield, Weston Park Hospital, Sheffield qClinical Oncology Department, Royal Cornwall Hospitals rSt. James's Institute of Oncology, St. James's University Hospital, Leeds, UK. ·Melanoma Res · Pubmed #26225580.

ABSTRACT: Before licensing, ipilimumab was first made available to previously treated advanced melanoma patients through an expanded access programme (EAP) across Europe. We interrogated data from UK EAP patients to inform future clinical practice. Clinicians registered in the UK EAP provided anonymized patient data using a prespecified variable fields datasheet. Data collected were baseline patient characteristics, treatment delivered, toxicity, response, progression-free survival and overall survival (OS). Data were received for 193 previously treated metastatic melanoma patients, whose primary sites were cutaneous (82%), uveal (8%), mucosal (2%), acral (3%) or unknown (5%). At baseline, 88% of patients had a performance status (PS) of 0-1 and 20% had brain metastases. Of the patients, 53% received all four planned cycles of ipilimumab; the most common reason for stopping early was disease progression, including death from melanoma. Toxicity was recorded for 171 patients, 30% of whom experienced an adverse event of grade 3 or higher, the most common being diarrhoea (13%) and fatigue (9%). At a median follow-up of 23 months, the median progression-free survival and OS were 2.8 and 6.1 months, respectively; the 1-year and 2-year OS rates were 31 and 14.8%, respectively. The 2-year OS was significantly lower for patients with poorer PS (P<0.0001), low albumin concentrations (P<0.0001), the presence of brain metastases (P=0.007) and lactate dehydrogenase levels more than two times the upper limit of normal (P<0.0001) at baseline. These baseline characteristics are negative predictors of benefit from ipilimumab and should be taken into consideration before prescription.

8 Minor Infliximab for IPILIMUMAB-Related Colitis-Letter. 2015

Arriola, Edurne / Wheater, Matthew / Karydis, Ioannis / Thomas, Gareth / Ottensmeier, Christian. ·Southampton NIHR Experimental Cancer Medicine Centre, Faculty of Medicine, University of Southampton Tremona Road, Southampton, United Kingdom. University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, United Kingdom. e.arriola-aperribay@soton.ac.uk. · University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, United Kingdom. · Southampton NIHR Experimental Cancer Medicine Centre, Faculty of Medicine, University of Southampton Tremona Road, Southampton, United Kingdom. University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, United Kingdom. ·Clin Cancer Res · Pubmed #26672088.

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