Lynn Schuchter, MD

DISCUSSANT LYNN SCHUCHTER, MD, the C. Willard Professor of Medicine at the Abramson Cancer Center at the University of Pennsylvania, Philadelphia, said the findings herald “a new era on two fronts…. Systemic therapy as initial treatment for patients with asymptomatic central nervous system (CNS) melanoma metastases is an important new option for our patients and is practice-changing, and sharing and revisiting discussions about prognosis are essential for all of our patients with advanced melanoma.” 

Noting intracranial disease control rates of at least 75% in the COMBI-MB trial, 60% in CheckMate 204, and 50% in the Australian Anti–PD-1 (programmed cell death protein 1) Brain Collaboration (ABC) trial, she commented, “These studies report fantastic results.” 

The optimal sequence of treatments is not yet clear, but it is likely that nivolumab (Opdivo) plus ipilimumab (Yervoy) or nivolumab alone, followed by BRAF/MEK inhibition at progression, would be better than the reverse, to which only 16% of patients in the ABC trial responded, she said. The manner in which systemic and local therapies should be combined is also not yet known. 

Although there is some concern about the timing of radiation and surgery with regard to targeted therapy, immunotherapy, in general, appears to be safe when combined with radiation, and the dual modalities may enhance the treatment effect, Dr. Schuchter said. 

While acknowledging the modest sample sizes and early results of these studies, she concluded, “The data are sufficient to warrant upfront treatment for asymptomatic patients with CNS metastasis.” ■

DISCLOSURE: Dr. Schuchter reported a consulting or advisory role with Incyte.