ASCO 2017: Nivolumab Plus Ipilimumab Effective Against Melanoma Brain Metastases

Patients with asymptomatic melanoma brain metastases may benefit from treatment with nivolumab plus ipilimumab

medwireNews: Two studies presented at the 2017 American Society of Clinical Oncology annual meeting in Chicago, Illinois, USA, suggest that patients with asymptomatic melanoma brain metastases respond well to treatment with nivolumab plus ipilimumab.

The first study – the Anti-PD1 (programmed cell death protein 1) Brain Collaboration (ABC) – recruited patients (median age 60 years, 77% male) naïve to anti-PD-1/programmed cell death ligand 1 (PD-L1)/PD-L2/cytotoxic T-lymphocyte antigen 4 therapy. They were randomly assigned to receive nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, every 3 weeks for 4 cycles followed by nivolumab 3 mg/kg every 2 weeks (n=26), or to receive the higher dose of nivolumab alone (n=25).

A third cohort of 16 patients who had failed local therapy, were neurologically symptomatic or had leptomeningeal disease also received nivolumab 3 mg/kg every 2 weeks.

The researchers found that 42% of patients who received nivolumab plus ipilimumab had an intracranial RECIST response, compared with 20% of those who received nivolumab alone and just 6% of the group with symptomatic brain metastases, leptomeningeal metastases or previous local therapy. Respective intracranial 6-month progression-free survival (PFS) rates were 46%, 28% and 13%.

Among treatment-naïve patients receiving nivolumab plus ipilimumab and nivolumab alone, the intracranial response rates were 50% and 21%, respectively, but dropped to 16% in patients who had previously received BRAF or MEK inhibitors, regardless of the treatment allocation.

Author Georgina Long, from the University of Sydney in New South Wales, Australia, said that there were no unexpected toxicities or treatment-related deaths.

She concluded: “Nivolumab combined with ipilimumab has high activity in melanoma brain metastases and may be considered for upfront therapy in such patients.”

The second study, CheckMate 204, conducted by Hussein Tawbi, from The University of Texas MD Anderson Cancer Center, in Houston, USA, and colleagues investigated the efficacy of the same nivolumab plus ipilimumab combined regimen in 75 patients (median age 59 years, 71% male) with at least one measurable melanoma brain metastasis (0.5–3.0 cm in diameter) and no neurological symptoms or steroid treatment.

The objective response rate at a median follow-up time of 9.2 months was 55%, with 21% achieving a complete response. The median time to response was 2.8 months and the median response duration and PFS had not yet been reached. At 6 months, however, PFS was 67%.

In both studies, extracranial responses were largely concordant with intracranial findings, and the rate of grade 3–4 treatment-related adverse events among patients receiving both drugs was also similar, at 46% in ABC and 52% in CheckMate 204.

Hussein Tawbi concluded: “The favorable safety and high anti-melanoma activity of [nivolumab plus ipilimumab] may represent a new [treatment] paradigm for [patients] with asymptomatic [melanoma brain metastases] and could change practice to avoid or delay whole brain [radiotherapy] or [stereotactic radiotherapy].”


Long GV, Atkinson V, Menzies AM, et al. A randomized phase II study of nivolumab or nivolumab combined with ipilimumab in patients (pts) with melanoma brain metastases (mets): The Anti-PD1 Brain Collaboration (ABC). J Clin Oncol; 35: 2017 (suppl; abstr 9508).

Tawbi HA-H, Forsyth PAJ, Algazi AP, et al. Efficacy and safety of nivolumab (NIVO) plus ipilimumab (IPI) in patients with melanoma (MEL) metastatic to the brain: Results of the phase II study CheckMate 204. J Clin Oncol; 35: 2017 (suppl; abstr 9507).

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