Overall survival (OS) for patients with melanoma brain metastasis treated at Memorial Sloan Kettering Cancer Center has increased significantly over the past five years, up to 13 months, according to our research published recently in Cancer.1 This increased OS duration, much higher than the historical survival of four to six months,2–6 can be traced to advances in targeted therapies and immunotherapies, as well as increased use of surgery and stereotactic radiosurgery (SRS), where needed.1
Numerous advances in targeted therapies for melanoma, including BRAF and MEK inhibitors and the checkpoint inhibitors ipilimumab, nivolumab, and pembrolizumab, have led to significant OS improvements in patients with metastatic melanoma.7–15 Further, studies have found that patients with melanoma brain metastasis respond to many of these therapies.16–21 For example, 58% of patients with BRAF V600E-positive melanoma brain metastases responded to combination treatment with dabrafenib and trametinib in the COMBI-MB trial (NCT02039947),20 and 46% to 57% of patients with untreated active brain metastases showed intracranial benefit to the combination of nivolumab and ipilimumab in the ABC (NCT02374242) and CheckMate 204 (NCT02320058) trials, respectively.19, 21
MSK researchers pioneered BRAF and MEK inhibitors, the use of immunotherapy in melanoma patients, and brain SRS, which is associated with significantly improved local control rates, fewer cognitive side effects, and improved quality of life for patients with brain metastasis than whole brain irradiation.22, 23 Today, more clinical trials are beginning to include patients with melanoma brain metastasis. Yet little data exists on how current treatments have affected survival or revealed prognostic factors associated with better or worse survival.
We conducted a retrospective study of 425 patients with 2,488 melanoma brain metastases diagnosed and managed with multimodality treatment at MSK between 2010 and 2019. Median OS was 8.9 months. However, patients diagnosed between 2015 and 2019 experienced a significantly longer OS of 13 months, compared with only 7 months for those diagnosed between 2010 and 2014 (P = 0.0003). The one-year survival rate was 52.4 percent for patients diagnosed in the latter five years, compared with 35.1% for those diagnosed in the earlier five years (P = 0.0003), with a median follow-up of 1.7 years for survivors in the latter group.1
Our empirically derived cutoff for the most significant increase in survival between 2014 and 2015 coincided with the US Food and Drug Administration’s approval of PD-1 blockade with nivolumab and pembrolizumab, and the subsequent approvals of the combinations ipilimumab plus nivolumab, dabrafenib plus trametinib, and vemurafenib plus cobimetinib.1
Worse prognosis was significantly associated with the number of metastases at diagnosis, previous receipt of immunotherapy, leptomeningeal dissemination, elevated serum levels of lactate dehydrogenase, and the presence of extracranial disease. Patients who underwent craniotomy had an improved survival (P = 0.01), likely reflecting appropriate patient selection for invasive procedures. The use of various central nervous system–directed and systemic therapies was associated with presenting symptoms, year of diagnosis, number and size of brain metastases, and the presence of extracranial disease.1
“Our study confirms the prognosis for MSK patients with melanoma brain metastasis has improved in the era of targeted therapies and immunotherapies, especially in the last five years,” said Nelson Moss, MD, a neurosurgeon who coheads MSK’s Multidisciplinary Brain Metastasis Clinic and performs about 150 brain metastasis resection surgeries annually, in addition to removal of other brain tumor types. “These improvements in survival also reflect MSK’s multimodal approach to treatment, including the use of craniotomy and SRS to augment cancer-directed systemic therapies, where needed.”
MSK is currently planning “window of opportunity” studies in collaboration with pharmaceutical companies to look for new ways to improve outcomes further. Patients scheduled for brain surgery will have the opportunity to volunteer to receive a targeted drug beforehand. Researchers will then analyze resected tumors to see whether a drug or combination therapy crossed the blood-brain barrier and elicited a response. “This innovative approach may allow us to see if a systemic blood level corresponds to a response in brain metastases in a small number of patients, much faster than if we enrolled 50 patients and waited years until the end of their life expectancy,” Dr. Moss said. “If so, there will be significant benefits in terms of greatly advancing research timelines and providing earlier guidance on which drugs or combination therapies should be developed further and studied in clinical trials.”
At MSK, dedicated radiation oncologists, neurosurgeons, neuroradiologists, medical oncologists, and physiatrists provide care exclusively in our Multidisciplinary Brain Metastasis Clinic. They collaborate to create a customized and centralized treatment plan for each patient, ensuring multimodality treatments are delivered in the best order, as quickly as possible, for the greatest benefits.
MSK treats a large volume of patients with brain metastases annually on expedited timelines and is one of few centers with the most advanced diagnostic and treatment options for these patients. We offer expedited day-1 treatment for patients needing immediate attention, including same-day radiation oncology counseling, CT simulation with mask fitting, radiation treatment planning, and SRS delivery.
To refer a patient, call 212-619-5837, and we can help set up an appointment within 48 hours.