The combination of nivolumab with ipilimumab is an effective treatment option for patients with advanced melanoma with asymptomatic brain metastases and should be considered for first-line therapy according to the study results published in Neuro-Oncology.
Treatment options for patients with melanoma with brain metastases are limited, and patients with active brain metastases are often excluded from clinical trials. Previously, the combination of nivolumab plus ipilimumab resulted in an intracranial response rate of 55% in patients with melanoma and asymptomatic brain metastases.
In this study, researchers reported the results of the combined immunotherapy in symptomatic and / or patients treated with corticosteroids at the time of introduction of treatment, as well as expanded follow-up data for the entire asymptomatic cohort.
This open-label, non-randomized phase II study included adults with histologically confirmed melanoma and evidence of brain metastases between 0.5 and 3.0 cm on magnetic resonance imaging of the brain. The study researchers classified the participants as asymptomatic (Cohort A) or as patients with stable neurological symptoms and / or corticosteroids (Cohort B).
All patients received a combination of nivolumab (1 mg / kg) and ipilimumab (3 mg / kg) for 4 doses every 3 weeks. They then received nivolumab monotherapy at 3 mg / kg every 2 weeks. Treatment lasted at least 6 months and continued until disease progression, unacceptable toxicity, or 24 months.
The primary endpoint was intracranial clinical benefit rate, including complete response, partial response, or stable disease for at least 6 months.
The sample included 18 patients with symptomatic brain metastases treated with corticosteroid in Cohort B and 101 patients with corticosteroid-free patients with asymptomatic brain metastases in Cohort A.
The median follow-up for patients in Cohort B was 5.2 months and patients received a median of 1 combination dose. The intracranial response was reported in 4 of 18 patients with an objective response rate of 22.2% for intracranial, extracranial and global diseases. Responses were seen in 2 of 12 corticosteroid-treated patients and 2 of 6 patients with symptomatic brain metastases.
The median progression-free survival in symptomatic patients was 1.2 months (95% CI, 0.7-1.3) for intracranial disease, and the median overall survival was 8.7 months (95% CI, 1.8-not reached) .
Data on the longer follow-up time of 101 patients with asymptomatic brain metastases (median follow-up time 20.6 months) confirmed the long-term effectiveness of the combination treatment with a clinical benefit rate of 58.4% (59 of 101 patients). The median duration of response, progression-free survival, and overall survival were not achieved.
The study had several limitations, including the lack of an independent review of the imaging data, the small sample size, and the exclusion of patients with unstable neurological symptoms, recent seizures, or a higher corticosteroid dose requirement.
“Based on our long-term follow-up data from Cohort A, we believe that the standard of care for patients with advanced melanoma with asymptomatic brain metastases who are candidates for immunotherapy should be 1 mg / kg nivolumab plus 3 mg / kg ipilimumab” he concluded the study researchers.
Disclosure: Some of the study’s authors stated links with biotech, pharmaceutical, and / or device companies. For a full list of the authors’ information, see the original reference.
Tawbi HA, Forsyth PA, Hodi FS et al. Safety and efficacy of the combination of nivolumab plus ipilimumab in patients with melanoma and asymptomatic or symptomatic brain metastases (CheckMate 204). Neuro Oncol. Published online April 21, 2021. doi: 10.1093 / neuonc / noab094