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Real-life data for first-line combination immune-checkpoint inhibition and targeted therapy in patients with melanoma
Marie-Luise Hilbers1, Florentia Dimitriou1, Peter Lau2
1Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
Background:
Melanoma brain metastases (MBM) have a poor prognosis. Systemic treatments that have improved outcomes in advanced melanoma have been shown to have an intracranial (IC) effect. We studied the efficacy and outcomes of combined immune checkpoint inhibitor ipilimumab/nivolumab (Combi-ICI) or targeted therapy (Combi-TT) as first-line treatment in MBM.
Methods:
MBM patients treated with Combi-ICI or Combi-TT within 3 months after MBM diagnosis. Endpoints were progression-free survival (PFS) and overall survival (OS).
Results:
53 patients received Combi-ICI, 32% had symptomatic MBM and 33.9% elevated LDH. 71.7% required local treatment. The disease control rate was 60.3%. IC response rate (RR) was 43.8% at 3-months with durable responses at 6- (46.5%) and 12-months (53.1%). Extracranial (EC) RR was 44.7% at 3-months and 50% at 12-months. Median PFS was 9.6 months (95% CI 3.6-NR) and median overall survival (mOS) 44.8 months (95% CI; 26.2-NR). 63 patients received Combi-TT, 55.6% of patients had symptomatic MBM, 57.2% of patients had elevated LDH and 68.3% of patients required local treatment. The disease control rate was 60.4%. ICRR was 50% at 3-months, but dropped at 6-months (20.9%). ECRR was 69.2% at 3-months and 17.6% at 12-months. Median PFS was 5.8 months (95% CI 4.2-7.6) and mOS 14.2 months (95% CI 8.99-26.8). In BRAFV600 patients, 26.7% of patients received Combi-ICI and 73.3% Combi-TT with OS (p = 0.0053) and mPFS (p = 0.03) in favour to Combi-ICI.
Conclusion:
Combi-ICI showed prolonged mOS with sustainable IC and EC responses. Despite the initially increased efficacy, Combi-TT responses at 12 months were low. Combi-ICI appeared superior to Combi-TT for OS and PFS in BRAFV600 patients. Other clinical factors are determinants for first-line treatment choice.
Insights
Combined immune checkpoint inhibitors (Combi-ICI) demonstrated superior overall survival and progression-free survival compared to combined targeted therapy (Combi-TT) for melanoma brain metastases. Combi-ICI also showed more durable intracranial and extracranial responses.
Area of Science:
- Oncology
- Neuro-oncology
- Immunotherapy
Background:
- Melanoma brain metastases (MBM) present a significant challenge with poor prognosis.
- Systemic treatments for advanced melanoma are showing efficacy within the brain.
- The study evaluates first-line treatment options for MBM.
Purpose of the Study:
- To compare the efficacy and outcomes of combined immune checkpoint inhibitor (Combi-ICI) versus combined targeted therapy (Combi-TT) as first-line treatment for melanoma brain metastases.
- To assess progression-free survival (PFS) and overall survival (OS) in MBM patients receiving these treatments.
Main Methods:
- Retrospective study of MBM patients treated with Combi-ICI or Combi-TT within 3 months of diagnosis.
- Endpoints included progression-free survival (PFS) and overall survival (OS).
- Analysis of intracranial (IC) and extracranial (EC) response rates at 3, 6, and 12 months.
Main Results:
- Combi-ICI (n=53) showed a median OS of 44.8 months and median PFS of 9.6 months, with durable IC and EC responses.
- Combi-TT (n=63) showed a median OS of 14.2 months and median PFS of 5.8 months, with initial high response rates that declined by 12 months.
- In BRAFV600 patients, Combi-ICI was superior to Combi-TT for OS (p=0.0053) and PFS (p=0.03).
Conclusions:
- Combined immune checkpoint inhibitors (Combi-ICI) offer prolonged overall survival and sustained intracranial/extracranial responses in melanoma brain metastases.
- Combined targeted therapy (Combi-TT) shows a decline in response rates by 12 months.
- Combi-ICI appears superior for BRAFV600 melanoma brain metastases, though other clinical factors influence first-line treatment decisions.
