medwireNews: Among individuals with melanoma brain metastases (MBMs) who have received prior PD-1 inhibitor therapy, treatment with nivolumab plus ipilimumab achieves an intracranial response in about one in 10, indicate findings.
“Local therapies, particularly radiotherapy, therefore, may be critical for these patients,” say Michael Postow and colleagues from Memorial Sloan Kettering Cancer Center in New York, USA, in a research letter published in JAMA Oncology.
Outlining the rationale for the study, they explain that although intracranial response rates to nivolumab plus ipilimumab range from 44% to 54% among patients who have no prior exposure to anti-PD-1 therapy, the efficacy of the combination in those with such exposure “remains unknown.”
The team continue: “With increasing use of neoadjuvant and adjuvant anti-PD-1 therapy and high incidence of MBMs, clinicians will frequently encounter the challenge of managing MBMs in patients with prior anti-PD-1 exposure.”
To address this, the researchers identified 28 patients (61% men) who received nivolumab–ipilimumab at their institution between January 2011 and December 2023 for one or more progressive MBMs of at least 5 mm in size. The participants were aged a mean of 64 years and the majority (64%) had previously received anti-PD-1 monotherapy, while 36% had additionally received ipilimumab, but none had received local therapy for MBMs.
Following treatment with nivolumab plus ipilimumab, and a median follow-up of 7 months, the intracranial objective response rate was 11%, comprising two complete responses and one partial response.
“Both patients with [complete response] had 2 or fewer intracranial lesions, had no prior ipilimumab exposure, and remained alive and intracranial- and extracranial-progression free with 3 and 28 months of follow-up as of data cutoff,” note Postow and associates.
Stable disease was the best intracranial response in 18%, but stability did not last more than 6 months in any of these patients, and71% of patients had intracranial progressive disease.
The median duration of intracranial progression-free survival was 1.6 months, and median overall survival was 6.7 months.
Postow et al say that “[t]he study’s modestly sized, single-center patient population limits definitive conclusions, especially around whether prior ipilimumab in some patients affected subsequent ipilimumab-nivolumab effectiveness.”
And they conclude: “This study also emphasizes the need for larger studies and clinical trials to improve therapies for patients with anti–PD-1–resistant progressive MBM.
“This question will be increasingly relevant with increasing use of adjuvant and neoadjuvant anti–PD-1 therapy in melanoma and other cancers.”
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