Alexander Menzies, MD
The combination of nivolumab (Opdivo) and ipilimumab (Yervoy) showed an intracranial response (ICR) rate of 46% for asymptomatic patients with melanoma brain metastases who had not received prior local therapy to the brain, according to the updated findings of the phase II ABC trial presented at the 2017 World Congress of Melanoma in Brisbane, Australia.
“Nivolumab combined with ipilimumab or nivolumab alone have activity in active, asymptomatic melanoma brain metastases without prior local therapy. Activity is higher when nivolumab and ipilimumab are given upfront,” said Alexander Menzies, MD, of the University of Sydney.
The ABC trial enrolled 76 patients with active melanoma brain metastases with at least 1 brain lesion that was greater than or equal to 5 mm but less than 40 mm. Additionally, patients had to have an ECOG performance status of 0 to 2. Prior BRAF and MEK inhibitors were allowed, whereas prior anti–PD-1/PD-L1 or anti–CTLA-4 therapy was not allowed. Patients serious autoimmune disease were excluded from the study.
There were 3 arms in the study. The first cohort (A) included 35 patients receiving nivolumab plus ipilimumab every 3 weeks for 4 cycles followed by nivolumab monotherapy every 2 weeks. The second cohort (B) included 25 patients randomized to nivolumab at the standard approved schedule. The third exploratory cohort of patients (C) included 16 patients with previous local treatment to the brain or with leptomeningeal disease. These patients were treated on nivolumab and could receive prednisone at <10 mg per dose.
The primary endpoint of the study was ICR. Secondary endpoints included extracranial response rate (ERR), overall response rate, progression-free survival (PFS), overall survival, and safety. The data cutoff was August 28, 2017. The median follow-up was 17 months.
Cohort A experienced 46% ICR with a complete response (CR) of 17%. Cohort B had an ICR rate of 20% with a CR of 12%. The ICR in cohort C was 6%. The median duration of response was not met. The ERR was 57% in cohort A, 29% in cohort B, and 29% in cohort C.
The median intracranial PFS rate has not been reached. The 6-month intracranial PFS rate for cohort A was 53% and 20% for cohort B. The median extracranial PFS was 13.8 months for cohort A, 2.6 months for cohort B, and 2.6 months for cohort C with 6-month PFS rates of 51%, 35%, and 19%, respectively. The median OS has not been reached. The 6-month OS rate was 78% in cohort A, 68% for cohort B, and 44% in cohort C.
Treatment-related adverse events (AEs) were experienced by 94% of patients in cohort A, 68% in cohort B, and 50% in cohort C. Treatment-related grade 3/4 AEs were experienced in 43% of patients in cohort A and in 20% and 6% of those in cohorts B and C, respectively. Discontinuations due to AEs occurred in 9%, 4%, and 0% of patients in cohorts A, B, and C, respectively. There were no new or unexpected toxicities, according to Menzies.
“Nivolumab combined with ipilimumab has high activity in melanoma brain metastases and may be considered for upfront therapy in such patients,” explained Menzies. “A clinical trial adding radiotherapy to those who progressed early on with nivolumab and ipilimumab is planned.”
Long GV, Atkinson V, Menzies AM, et al., Randomized phase II study of nivolumab (nivo) or nivo plus ipilimumab (ipi) in patients (pts) with melanoma brain metastases (mets): Anti-PD-1 Brain Collaboration (ABC). Presented at: 2017 World Congress of Melanoma; October 18-21, 2017; Brisbane, Australia. Presentation SMR09-6.
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