Frequent Use of Local Therapy Underscores Need for Multidisciplinary Care in the Management of Patients With Melanoma Brain Metastases Treated With PD-1 Inhibitors

Abstract

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. Twenty-three 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 1 untreated or progressive brain metastasis, 5 to 20 mm in size, without any associated neurologic symptoms. Local therapy (stereotactic radiosurgery, surgery, or laser interstitial thermal therapy) was used to treat concerning lesions immediately before 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 or during the trial-4 patients received local therapy before the trial owing to lesion size or location in sensitive areas; 6 during the trial because of tumor growth, hemorrhage, or radiation necrosis/cystic changes; and 3 both before and during the trial. Of the 10 patients who did not receive local therapy immediately before or during the trial, 8 patients (35%) did not later receive local therapy owing to rapid disease progression, and only 2 patients (9%) lived for 2 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 neurologic safety.