Limited benefit of immunotherapy for symptomatic melanoma patients with brain metastasis

December 2021 Cancer trials Nalinee Pathak

In recent years, immunotherapy and targeted therapies have changed the treatment landscape for melanoma patients without brain metastasis, resulting in a significant decline in mortality due to the disease. Still, around one third of melanoma patients are diagnosed with brain metastasis, and the remaining two thirds can develop it during the disease.  Despite available therapeutic approaches such as surgery or radiation, treatment outcomes remain very poor.

Investigators from the university of Texas MD Anderson Cancer Center (USA) have earlier reported on the efficacy of immunotherapy combination of nivolumab and ipilimumab in melanoma patients with brain metastasis (MBM). The combination provided a 55% intracranial response rate in asymptomatic MBM patients. The researchers have recently reported the efficacy of this immune therapy combination for symptomatic patients. 

CHECKMATE 204 trial

CHECKMATE 204 is an open-label phase II study designed to evaluate the efficacy of immunotherapy combination in MBM patients. Eligible patients (aged ≥18 years with histologically confirmed melanoma) were enrolled in either cohort A i.e., asymptomatic patients, or in cohort B i.e., symptomatic patients (stable neurological symptoms and/or receiving corticosteroids). Four dosages of nivolumab (1mg/kg) plus ipilimumab (3 mg/kg) were given to patients every three weeks, followed by 3 mg/kg, nivolumab, every 2 weeks until progression, unacceptable toxicity, or 24 months. The primary endpoint of the study was the intracranial clinical benefit rate (CBR).

Results

The immune combination (median one dose) provided an intracranial CBR of 22.2% in symptomatic (n=18) patients. Out of 12 patients, two on corticosteroids and six not on corticosteroids had a complete response (CR). In symptomatic patients with MBM, the median intracranial progression-free survival (PFS) was 1.2 months, and overall survival (OS) was 8.7 months. At a longer median follow-up of 20.6 months, the intracranial CBR of 58.4% was observed in asymptomatic patients (n=101). The PFS, OS, and median duration of response were not reached. No new treatment-related toxicity was observed.

Conclusion

The combination of nivolumab plus ipilimumab provides significant clinical benefits for asymptomatic MBM patients and thus should be considered for first-line therapy. However, the benefits of this combination are limited for symptomatic MBM. Therefore, alternative treatment approaches are needed for this group of MBM patients.  

Reference

Tawbi HA, Forsyth PA, Hodi FS, Lao CD, et al. Safety and efficacy of the combination of nivolumab plus ipilimumab in patients with melanoma and asymptomatic or symptomatic brain metastases (CheckMate 204). Neuro Oncol. 2021 Nov 2;23(11):1961-1973. doi: 10.1093/neuonc/noab094. PMID: 33880555; PMCID: PMC8563325.

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