Douglas Kondziolka, MD
Approximately 30% of patients with melanoma will develop brain metastases; however, with the advancements of precise radiosurgery as well as combination systemic therapies, survival outcomes are improving.
For example, results from the phase II Anti-PD1 Brain Collaboration trial that were presented at the 2017 ASCO Annual Meeting demonstrated that the combination of nivolumab (Opdivo) plus ipilimumab (Yervoy) led to a 42% intracranial response (ICR) rate in asymptomatic patients with melanoma brain metastases who had not received prior local therapy to the brain.1
The 6-month intracranial progression-free survival rate was 46% with the anti–PD-1/CTLA-4 combination.
Exciting findings from the phase II COMBI-MB trial were also presented at the meeting, showing that the BRAF/MEK inhibitor combination of dabrafenib (Tafinlar) plus trametinib (Mekinist) led to an ICR rate of 58% in patients with melanoma that had metastasized to the brain.2
“[With] what was often one of the worst cancers to spread to the nervous system, patient outcomes are [now] improving and we are very excited about that,” said Douglas Kondziolka, MD.
Kondziolka, a professor of neurosurgery at NYU Langone Medical Center in New York, shared insight on some of the technical advancements in treating brain metastases in patients with melanoma during an interview at the 2017 OncLive®
State of the Science Summit on Melanoma and Immuno-Oncology.
OncLive: Please discuss the highlights of your presentation on brain metastases.
: Brain metastases are a very common cancer and, unfortunately, [are something] that means a lot for the patient and their family. A patient with cancer, whether it be melanoma or any type of cancer, is battling it and, hopefully, successfully. If they get the news that the cancer is now in the brain or spinal cord, that’s a scary thing. It means it could potentially affect function, who they are, what they are about, their ability to walk, memory, speech, and vision. It means a lot and, often, they are aware of the fact that if the cancer is in the brain, sometimes that affects survival.
Typically, in the last 50 years since we began treating metastatic tumors [in the brain], the treatments have been surgery for large tumors. Sometimes, it is whole-brain radiation, which is a scary thought because the normal brain is being radiated—not just the tumor.
More recently, we have what is called radiosurgery, which is precise focal radiation, and that has been the thing to do for small brain metastases. What is interesting in melanoma and other cancers is this new era of drug therapy approaches. These can either help through the immune system or the cancer cells themselves to limit the spread through the brain and work together with focused radiation to provide better outcomes.
What is the prevalence of patients with melanoma who have brain metastases?
For patients with advanced melanoma, about 30% of them will eventually have a site in the brain. That is common—more common than in lung cancer or certain types of breast cancer. Because of that, there has been a deeper awareness from melanoma oncologists to think about the brain as a potential site.
Even if a patient doesn’t have a neurologic problem, melanoma is the first cancer where staging brain scans were obtained—a good-quality MRI to see if something was there. If the tumor was there, hopefully it would be small and could be taken care of effectively. Melanoma tumors often went to the nervous system, so melanoma oncologists were among the first to be thinking about that possibility.
We saw results of combination systemic therapy for various patient populations at the 2017 ASCO Annual Meeting. Can you comment on these data?
Patients with BRAF
-mutant melanoma, who are usually on a targeted therapy, can develop brain metastases despite being on that [treatment]. Sometimes tumors grow nevertheless, and we will then treat them with focused radiation or, if it’s large, tumor removal. In the patients on immunotherapy, if the tumor develops in the brain, focused radiation or radiosurgery can be very effective.
One of the differences between those 2 types of treatment is what happens to the brain tumor. The goal of the radiation therapy is to damage and injure the tumor. Of course, with any injury in the body, it is mediated through inflammation. If the immune system is energized through immunotherapy, one might expect a more prominent inflammatory response as the tumor is dying. If this is in the brain, that can lead to swelling there. If it’s in a functional location, that can lead to an arm weakness or some speech trouble; sometimes, corticosteroid therapy is needed.