Author(s)
Borget I1, Dalle S2, Leccia M3, Dutriaux C4, Stoebner P5, Dalac S6, Aubin F7, Saiag P8, Lacour JP9, Lesimple T10, Dupuy A11, Mortier L12, Beylot-Barry M13, Maubec E14, Descamps V14, Lok C15, Stephan A16, Guillot B17, de Quatrebarbes J18, Dreno B19, Gally S20, Mouri M20, Allayous C21, Kowal A21, Porcher R22, Lebbe C21
1Univ Paris-Sud, Faculty of Pharmacy, GRADES, Châtenay-Malabry, France, 2Hospices Civils de Lyon Hospital, Cancer research center of Lyon, Lyon, France, 3Hôpital Albert Michallon - CHU de Grenoble, LA TRONCHE, France, 4Bordeaux Saint-André Hospital, Bordeaux, France, 5Nîmes Hospital, Nîmes, France, 6Dijon Hospital, Dijon, France, 7Besançon Hospital, Besançon, France, 8Ambroise Pare Hospital, Boulogne Billancourt, France, 9CHU de Nice - Hôpital l'Archet 2, NICE CEDEX 3, France, 10CLCC Rennes Eugene Marquis, Rennes, France, 11Rennes Hospital, Rennes, France, 12Lille Hospital, Lille, France, 13Bordeaux Haut-Leveque Hospital, Bordeaux, France, 14Bichat Hospital, Paris, France, 15Amiens Hospital, Amiens, France, 16Caen Hospital, Caen, France, 17Montpellier Hospital, Montpellier, France, 18Annecy Genevois Hospital, Annecy, France, 19Centre Hospitalier Universitaire, Nantes Cedex 1, France, 20Roche S.A.S., Boulogne Billancourt, France, 21Saint-Louis Hospital, Paris, France, 22Center for Clinical Epidemiology, Hotel-Dieu Hospital, Paris, France
OBJECTIVES: Vemurafenib is the first BRAF inhibitor indicated in unresectable or metastatic melanoma. French Real World Data, notably regarding use, effectiveness and safety of vemurafenib, were expected from Roche (Market Authorisation Holder, MAH) by the French Health Care Payer. METHODS: MELBASE is a national, multicenter and non-interventional cohort promoted by Paris public hospitals and INCa since 2012, collecting clinical data of patients with unresectable or metastatic melanoma. Data extracted from MELBASE on patients treated with vemurafenib monotherapy were collected from March 2013 to September 2015. Overall survival (OS, primary criterion) and progression-free survival (PFS) were estimated using the Kaplan Meier method. Prognostic factors of patients’ survival were assessed using univariate and multivariate Cox models. External validity of study results was checked through Roche exhaustive data on vemurafenib distribution to community pharmacies. RESULTS: Extracted data from 101 patients included by 18 centers were analyzed: men (60%), mean age (59±15 years), ECOG <2 (78%), disease stage IV (93%), M1c stage (66%), V600E mutation (70%). Vemurafenib was prescribed as first-line treatment in 88% of patients for a median duration of 3.9 months (Q1-Q3: 1.8-6.6). Median OS was 12.0 months (CI 95%: 9.5-18.3) in the whole population, 14.8 months (11.2-not reached) if first-line treatment, and 7.5 months (4.8-nr) if ≥2 lines. Median PFS was 5.4 months (4.4-6.6) in all. M1c stage, symptomatic brain metastases, and vemurafenib starting at ≥2 lines were associated with shorter survival. Over treatment duration, 408 toxicities were reported in 88 patients (87%), including 330 vemurafenib-related toxicities (87 patients, 86%) and 24 serious toxicities (18 patients, 18%). No toxicity-related deaths were reported. CONCLUSIONS: An effective collaboration between institution and MAH has been set up to provide evidence, in appropriate timelines, to Payer. Results from clinical development were supported with analysis performed on Real World Data from preexisting academic database.
