title: Ipilimumab in the real world: the UK expanded access programme experience in previously treated advanced melanoma patients.
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.
authors.affiliation: 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.
authors.forename: Saif S
authors.initials: SS
authors.lastname: Ahmad
authors.forename: Wendi
authors.initials: W
authors.lastname: Qian
authors.forename: Sarah
authors.initials: S
authors.lastname: Ellis
authors.forename: Elaine
authors.initials: E
authors.lastname: Mason
authors.forename: Muhammad A
authors.initials: MA
authors.lastname: Khattak
authors.forename: Avinash
authors.initials: A
authors.lastname: Gupta
authors.forename: Heather
authors.initials: H
authors.lastname: Shaw
authors.forename: Amy
authors.initials: A
authors.lastname: Quinton
authors.forename: Jarmila
authors.initials: J
authors.lastname: Kovarikova
authors.forename: Kiruthikah
authors.initials: K
authors.lastname: Thillai
authors.forename: Ankit
authors.initials: A
authors.lastname: Rao
authors.forename: Ruth
authors.initials: R
authors.lastname: Board
authors.forename: Jenny
authors.initials: J
authors.lastname: Nobes
authors.forename: Angus
authors.initials: A
authors.lastname: Dalgleish
authors.forename: Simon
authors.initials: S
authors.lastname: Grumett
authors.forename: Anthony
authors.initials: A
authors.lastname: Maraveyas
authors.forename: Sarah
authors.initials: S
authors.lastname: Danson
authors.forename: Toby
authors.initials: T
authors.lastname: Talbot
authors.forename: Mark
authors.initials: M
authors.lastname: Harries
authors.forename: Maria
authors.initials: M
authors.lastname: Marples
authors.forename: Ruth
authors.initials: R
authors.lastname: Plummer
authors.forename: Satish
authors.initials: S
authors.lastname: Kumar
authors.forename: Paul
authors.initials: P
authors.lastname: Nathan
authors.forename: Mark R
authors.initials: MR
authors.lastname: Middleton
authors.forename: James
authors.initials: J
authors.lastname: Larkin
authors.forename: Paul
authors.initials: P
authors.lastname: Lorigan
authors.forename: Matthew
authors.initials: M
authors.lastname: Wheater
authors.forename: Christian H
authors.initials: CH
authors.lastname: Ottensmeier
authors.forename: Pippa G
authors.initials: PG
authors.lastname: Corrie
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D018450:Disease Progression; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006297:Health Services Accessibility / Q000592:standards; D006801:Humans; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D012189:Retrospective Studies; D016879:Salvage Therapy; D012878:Skin Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016019:Survival Analysis; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D000074324:Ipilimumab