In a single-center retrospective study reported in JAMA Oncology, Lochrin et al identified activity of ipilimumab/nivolumab in melanoma brain metastases after progression on anti–PD-1 treatment.
Study Details
The study involved 28 patients with prior PD-1 inhibitor treatment who developed progressive melanoma brain metastases and were treated with ipilimumab/nivolumab at Memorial Sloan Kettering Cancer Center between January 2011 and December 2023. Patients had to have one or more melanoma brain metastases (≥ 5 mm) and no prior receipt of local interventions (eg, stereotactic radiosurgery). The primary outcome of interest was intracranial objective response rate.
Key Findings
Overall, 18 patients (64%) received prior anti–PD-1treatment without ipilimumab, including 10 (56%) without other systemic treatment, and 10 (36%) received a PD-1 inhibitor plus ipilimumab. Median intracranial lesion size was 1.0 cm (interquartile range = 0.6–2.1 cm) and 18 patients (64%) had more than five intracranial lesions.
Median follow-up was 7 months (interquartile range = 4–29 months). Intracranial response was observed in three patients (11%, 95% confidence interval [CI] = 2%–28%), including complete response in two patients. The two patients with complete response were among four patients with two or more lesions, and neither one of the two had prior ipilimumab exposure; as of data cutoff, the two patients remained alive and intracranial and extracranial progression–free at 3 and 28 months of follow-up. All five patients with stable disease (18%) had stable disease of < 6 months.
The extracranial objective response rate was 14% (95% CI = 4%–33%). No patient with intracranial response had extracranial progression.
Median intracranial progression-free survival was 1.6 months (95% CI = 1.2–4.4 months). Among 27 patients with available data on subsequent treatment, 13 (48%) received local therapy and 8 (30%) received systemic therapy. Median overall survival among all patients was 6.7 months (95% CI = 3.6–10.0 months).
Conclusion
The investigators concluded: “To our knowledge, this study is first to report the intracranial effectiveness of ipilimumab/nivolumab in patients with progressive melanoma brain metastases after anti–PD-1 therapy, showing 11% intracranial [objective response rate], 1.6 months median intracranial [progression-free survival], and 6.7 months median [overall survival]. Local therapies, particularly radiotherapy, therefore, may be critical for these patients.”
Michael A. Postow, MD, Department of Medicine, Memorial Sloan Kettering Cancer Center, is the corresponding author for the JAMA Oncology article.
Disclosures: The study was funded by a grant from the National Cancer Institute. For full disclosures of all study authors, visit jamanetwork.com.
