An increasing number of clinical trials are studying immunotherapy for the treatment of brain metastases. The role of local therapy in this setting has not been well described.

23 melanoma patients with brain metastases were treated with pembrolizumab in a prospective phase 2 trial, NCT02085070, and included in this secondary analysis. Patients had at least one untreated or progressive brain metastasis, 5-20 mm in size, without any associated neurological symptoms. Local therapy (stereotactic radiosurgery, surgery, or laser interstitial thermal therapy) was used to treat concerning lesions immediately prior to trial enrollment and was also allowed on trial in patients whose brain metastases were progressing but who were otherwise deriving benefit.

In total, 13 out of 23 patients (57%) received local therapy immediately before and/or on trial - 4 to enter trial because of lesion size or location in sensitive areas, 6 while on trial for tumor growth, hemorrhage, or radiation necrosis/cystic changes, and 3 patients received local therapy both before and during the trial. Ten did not receive local therapy immediately before or on trial - eight (35%) because of rapid disease progression, while only two (9%) patients lived for two years without requiring any local therapy.

Local therapy continues to play an important role in the management of melanoma patients with brain metastases being treated with immunotherapy. These patients should be closely monitored via serial brain imaging, with a multidisciplinary team involved in clinical decision making to ensure each patient's neurological safety.