Nivolumab-ipilimumab combo improves outcomes in melanoma patients with brain metastases
The combination of nivolumab and ipilimumab may improve rates of intracranial clinical benefit, complete response, and partial response in patients with melanoma, according to a recent study.
“The results of our study show that systemic therapy with combined nivolumab and ipilimumab has clinically meaningful efficacy in patients with asymptomatic, untreated melanoma metastases to the brain,” said the researchers.
This open-label, multicentre, phase II trial involved 94 patients with melanoma (median age 59 years, 69 percent male) who had untreated brain metastases. Participants were given up to four doses of 1 mg/kg nivolumab and 3 mg/kg ipilimumab every 3 weeks in the induction phase. Of these, 55 patients were given 3 mg/kg nivolumab every 2 weeks during the maintenance phase. Patients continued treatment for a maximum of 24 months or until disease progression, unacceptable toxicity, or study withdrawal. [N Engl J Med 2018;379:722-730]
At a median follow-up of 14 months, the rate of intracranial clinical benefit (defined as patients with stable disease for at least 6 months) was 57 percent, with a complete response rate of 26 percent and a partial response rate of 30 percent, assessed according to the modified RECIST* criteria.
A subgroup analysis of patients with lactate dehydrogenase levels above vs below the upper limit of normal range showed a higher rate of intracranial clinical benefit (66.7 percent vs 50.9 percent).
A higher rate of intracranial clinical benefit was also observed in patients with tumour PD-L1 expression of ≥5 percent vs <5 percent (76 percent vs 48 percent).
The benefits were also evident regardless of target-lesion size (63.6, 55.1, 50.0, and 50.0 percent for <1 cm, ≥1 to <2 cm, ≥2 to <3 cm, and ≥3 cm, respectively).
The 6-month and 9-month progression-free survival rates were 64.2 percent and 59.5 percent, respectively, while the 6-month, 9-month, and 12-month overall survival rates were 92.3 percent, 82.8 percent, and 81.5 percent, respectively.
Treatment-related adverse events (AEs) of any grade occurred frequently (97 percent), with 55 percent of patients reporting grade 3 or 4 AEs.
“Most importantly, therapy with nivolumab plus ipilimumab prevented intracranial progression for more than 6 months in 64 percent of patients. These results are relevant in a population in whom progression can quickly result in substantial neurologic symptoms, functional impairment, and the need for glucocorticoid therapy,” the researchers said.
“Although this was a relatively small, nonrandomized study, in our view, the data reported are relevant to clinical practice, given the high response rate, rapid time to response, and manageable side-effect profile. Therefore, outside the context of clinical trials, we would suggest that this regimen be considered as first-line therapy for all patients with brain metastases who meet the inclusion criteria for this study,” wrote Dr Samra Turajlic and Dr James Larkin from The Royal Marsden NHS Foundation Trust in Chelsea, London, in an editorial. [N Engl J Med 2018;379:789-790]
*RECIST: Response Evaluation Criteria in Solid Tumors