Efficacy and safety of ipilimumab in patients with advanced melanoma and brain metastases

Abstract

Patients with melanoma brain metastases have a poor prognosis and historically have been excluded from clinical trials. The Expanded Access Program (EAP) provided an opportunity to evaluate the feasibility of ipilimumab (3 mg/kg every 3 weeks for four doses) in patients with stage 3 (unresectable) or 4 melanoma and asymptomatic brain metastases, who had failed or did not tolerate previous treatments and had no other therapeutic option available. Tumor assessments were conducted at baseline and week 12 using immune-related response criteria and patients were monitored for adverse events (AEs). Of 855 patients participating in the EAP in Italy, 146 had asymptomatic brain metastases. With a median follow-up of 4 months, the global disease control rate was 27 %, including 4 patients with a complete response and 13 with a partial response. Median progression-free survival and overall survival were 2.8 and 4.3 months, respectively and approximately one-fifth of patients were alive 1 year after starting ipilimumab. In total, 29 % of patients reported a treatment-related AE of any grade, which were grade 3/4 in 6 % of patients. AEs were generally reversible with treatment as per protocol-specific guidelines. Ipilimumab shows durable benefits in some patients with advanced melanoma metastatic to the brain, with safety results consistent with those previously reported in clinical trials.

Diagnosis and treatment of brain metastases from solid tumors: guidelines from the European Association of Neuro-Oncology (EANO)

“…A single arm phase II study, NIBIT-M1, treated 86 patients with ipilimumab and fotemustine, of whom 20 had asymptomatic brain metastases at baseline, mostly oligometastases 96 : 10 of these patients achieved disease control, and median PFS and OS were 4.5 months and 13.4 months, respectively. In an EAP study of stages 3 and 4 melanoma and asymptomatic brain metastases failing or not tolerating other treatments, 97 ipilimumab yielded a control rate of 27%, including 4 patients with CR and 13 with PR. Median PFS and OS were 2.8 and 4.3 months, respectively, and approximately one-fifth of patients were alive 1 year after starting ipilimumab.…”

Emerging findings into molecular mechanism of brain metastasis

“…When ipilimumab cooperated with SRS, a median survival was increased from 4.9 to 21.3 months, along with a 2‐year survival rate from 19.7% to 47.2% 119. Intracranial disease control rates are reported as 10% and 24% in patients with stable BM and those with asymptomatic BM respectively 120. Nivolumab and pembrolizumab, both of them against PD‐1, have gained durable clinical response in patients with advanced melanoma and metastatic NSCLC.…”

Traitement systémique des métastases cérébrales de mélanome

“…Cette approche paraissait cependant moins intéressante chez les patients de la classe RPA (recursive partitioning analysis) 3 et atteints d'une maladie systémique non contrôlée [22]. Dans la cohorte italienne, 146 patients atteints de métastases cérébrales asymptomatiques sans autres options thé-rapeutiques étaient traités par ipilimumab à la dose de 3 mg/kg toutes les 3 semaines [23]. Cent quarante-cinq patients ont finalement été évaluables (un patient était perdu de vue).…”