Single-center study under a French Temporary Authorization for Use (TAU) protocol for ipilimumab in metastatic melanoma: negative impact of baseline corticosteroids

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). Patients and 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). Conclusion: 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.