title: Single-center study under a French Temporary Authorization for Use (TAU) protocol for ipilimumab in metastatic melanoma: negative impact of baseline corticosteroids.
abstract: Ipilimumab is an anti-CTLA-4 antibody which has recently been approved in Europe as a monotherapy in the treatment of metastatic melanoma. We report a single-center study among patients treated within a Temporary Authorization for Use (TAU) protocol. We also performed a review of the literature involving expanded access program studies with a focus on factors associated with overall survival (OS).
  
  
  METHODS
  This retrospective, observational study included patients between June 2010 and July 2011 with a diagnosis of non-resectable stage III or IV melanoma with at least one previous line of chemotherapy. Treatment consisted of four courses of ipilimumab at a dose of 3mg/kg every three weeks.
  
  
  RESULTS
  45 patients were included, among whom 23 (51%) had brain metastases. 33 (71%) of the patients completed the induction phase. The best overall response rate (BORR) was 13% and median overall survival (OS) was 8 months (95%CI: 7 to 12). OS was not different between patients with brain metastases at baseline and those without (p = 0.10), regardless of BRAF V600E status (p = 0.61). OS was poorer in patients who were being treated with corticoids at baseline (p<0.001) or with LDH at baseline > 500 UI/ml (p = 0.008).
  
  
  CONCLUSIONS
  A subset of patients most likely to benefit from ipilimumab should be defined. In our series we found a negative association of baseline corticosteroids with OS. Unlike high LDH levels, BRAF V600 E status and brain metastases should not be barriers to the initiation of treatment.
authors.affiliation: APHP Department of Dermatology Hôpital Saint-Louis, 1, avenue Claude-Vellefaux. 75010 Paris, France; Université Paris 7-Diderot, INSERM U976.
authors.forename: François
authors.initials: F
authors.lastname: Chasset
authors.affiliation: APHP Department of Dermatology Hôpital Saint-Louis, 1, avenue Claude-Vellefaux. 75010 Paris, France; Université Paris 7-Diderot, INSERM U976.
authors.forename: Cécile
authors.initials: C
authors.lastname: Pages
authors.affiliation: APHP Department of Biostatistics and Medical Information, Hôpital Saint-Louis; ECSTRA Team, CRESS UMR 1153, INSERM, Paris Diderot University.
authors.forename: Lucie
authors.initials: L
authors.lastname: Biard
authors.affiliation: APHP Department of Dermatology Hôpital Saint-Louis, 1, avenue Claude-Vellefaux. 75010 Paris, France; Université Paris 7-Diderot, INSERM U976.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Roux
authors.affiliation: APHP Department of Dermatology Hôpital Saint-Louis, 1, avenue Claude-Vellefaux. 75010 Paris, France; Université Paris 7-Diderot, INSERM U976.
authors.forename: Irina
authors.initials: I
authors.lastname: Sidina
authors.affiliation: APHP Department of Pharmacy Hôpital Saint-Louis ; Université Paris 7-Diderot, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Madelaine
authors.affiliation: APHP Department of Dermatology Hôpital Saint-Louis, 1, avenue Claude-Vellefaux. 75010 Paris, France; Université Paris 7-Diderot, INSERM U976.
authors.forename: Nicole
authors.initials: N
authors.lastname: Basset-Seguin
authors.affiliation: APHP Department of Dermatology Hôpital Saint-Louis, 1, avenue Claude-Vellefaux. 75010 Paris, France; Université Paris 7-Diderot, INSERM U976.
authors.forename: Manuelle
authors.initials: M
authors.lastname: Viguier
authors.affiliation: APHP Department of Dermatology Hôpital Saint-Louis, 1, avenue Claude-Vellefaux. 75010 Paris, France; Université Paris 7-Diderot, INSERM U976.
authors.forename: Nika
authors.initials: N
authors.lastname: Madjlessi-EzrA
authors.affiliation: APHP Department of Dermatology Hôpital Saint-Louis, 1, avenue Claude-Vellefaux. 75010 Paris, France; Université Paris 7-Diderot, INSERM U976.
authors.forename: Pierre
authors.initials: P
authors.lastname: Schneider
authors.affiliation: APHP Department of Dermatology Hôpital Saint-Louis, 1, avenue Claude-Vellefaux. 75010 Paris, France; Université Paris 7-Diderot, INSERM U976.
authors.forename: Martine
authors.initials: M
authors.lastname: Bagot
authors.affiliation: APHP Department of Biostatistics and Medical Information, Hôpital Saint-Louis; ECSTRA Team, CRESS UMR 1153, INSERM, Paris Diderot University.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Resche-Rigon
authors.affiliation: APHP Department of Dermatology Hôpital Saint-Louis, 1, avenue Claude-Vellefaux. 75010 Paris, France; Université Paris 7-Diderot, INSERM U976.
authors.forename: Céleste
authors.initials: C
authors.lastname: Lebbe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D003952:Diagnostic Imaging; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D005602:France; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D007275:Injections, Intravenous; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D005938:Glucocorticoids; D000074324:Ipilimumab
keywords: baseline corticosteroids; ipilimumab; melanoma