medwireNews: Patients with melanoma and untreated, asymptomatic brain metastases benefit from treatment with a combination of nivolumab and ipilimumab, suggest the results of the ABC and CheckMate 204 trials.
Both studies were presented at the 2017 annual meeting of the American Society of Clinical Oncology, held in Chicago, Illinois, USA.
In the phase II ABC (Anti-PD1 Brain Collaboration) trial, 51 patients with asymptomatic brain metastases who had not previously received checkpoint inhibitor therapy were randomly assigned to receive nivolumab 1 mg/kg alongside ipilimumab 3 mg/kg every 3 weeks for four cycles, followed by nivolumab 3 mg/kg every 2 weeks, or to receive the higher dose of nivolumab as monotherapy.
During a median follow-up of 16.4 months, 42% of the 26 patients who received the combination achieved an intracranial RECIST response, as did 20% of the 25 participants given nivolumab alone. The corresponding complete response rates were 15% and 12%.
Intracranial progression-free survival (PFS) was a median of 4.8 and 2.7 months for the nivolumab plus ipilimumab and nivolumab monotherapy groups, respectively, with 6-month rates of 46% and 28%.
Of note, among those who responded to treatment, the responses were durable, with the median duration not reached at data lock in May 2017, said presenting author Georgina Long (University of Sydney, New South Wales, Australia). Furthermore, not one of the complete responders had progressed at the time of analysis, she added, and only a small proportion of those with a partial response had disease progression.
When stratified by receipt of prior BRAF or MEK inhibitor therapy, intracranial response rates were a respective 50% and 21% for patients who were naïve to such treatment in the combination and nivolumab alone arms, falling to 16% in either arm for those who had received BRAF or MEK inhibitors previously.
The study also included 16 patients with previously treated, symptomatic, or leptomeningeal intracranial disease – these patients received the 3 mg/kg regimen of nivolumab given alone. These patients did not appear to derive a benefit from treatment, with an intracranial response rate of 6% and 6-month PFS rate of 13%.
“Activity is high when nivolumab plus ipilimumab is given upfront”
Noting that “activity is high when nivolumab plus ipilimumab is given upfront,” Georgina Long concluded that the combination could be considered for the initial treatment of asymptomatic brain metastases in melanoma patients.
CheckMate 204, also a phase II trial, included 75 patients with at least one measurable and non-irradiated intracranial metastasis who were given the same nivolumab plus ipilimumab regimen used in the ABC trial.
Fifty-five percent of participants had an objective intracranial response during a median follow-up of 9.2 months, with 21% and 33% achieving a complete and partial response, respectively. A further 5% had stable disease, giving an intracranial clinical benefit rate of 60%.
Once again, responses were durable, with the median duration of response not reached among the 93% of patients with ongoing responses.
Median intracranial PFS had not been reached at the time of analysis, but the 6-month rate was 67%, which appeared to be stable up to 9 months, reported Hussein Tawbi (The University of Texas MD Anderson Cancer Center, Houston, USA) on behalf of his fellow investigators. The Kaplan–Meier curve for intracranial PFS seems to be plateauing, which is “quite promising,” he said.
The toxicity profile of the combination was as expected in both studies, with no new safety signals. Adverse effects of grade 3 or 4 attributable to treatment occurred in 46% and 52% of patients in the ABC and CheckMate 204 trials, respectively, with a comparable 27% and 31% discontinuing the combination due to toxicity.
The combination could “become a new treatment option” for this patient population...
Given the “favorable safety and high anti-melanoma activity,” the combination could “become a new treatment option” for this patient population, perhaps even changing practice to avoid or defer whole-brain or stereotactic radiotherapy, concluded Tawbi.
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