Immunotherapy and Radiation Combo Boosts Survival in Melanoma Patients With Brain Metastases

The combination of Opdivo (nivolumab) and radiation therapy may provide better disease control and a boost in overall survival (OS) in patients with melanoma whose disease has metastasized to the brain, compared with standard current treatment.

Researchers of Moffitt Cancer Center retrospectively analyzed data from 26 patients with 73 brain metastases from two separate clinical trials at the center. Radiation was administered prior to, during, and after Opdivo in 33 lesions (45 percent), five lesions (7 percent) and 35 lesions (48 percent), respectively.

According to study results, Kaplan-Meier estimates for local brain metastases control following radiation were 91 percent after six months and 85 percent after 12 months. Median OS from the date of stereotactic radiation and Opdivo initiation was 11.8 and 12.0 months, respectively, in patients receiving Opdivo for unresected disease. Median OS was not reached in patients treated in the resected setting.

“This is the first study to assess outcomes of [Opdivo] and stereotactic radiation for the management of brain metastases,” lead study author Kamran A. Ahmed, a resident in the Department of Radiation Oncology at Moffitt, said in an interview with CURE. “We found that overall survival and local control in this patient cohort was improved over historical controls, suggesting [Opdivo] and radiation may have a synergistic effect in the management of melanoma brain metastases.”

These findings are important, as there is a great need for improvement in the management of patients with melanoma brain metastases, Ahmed says. Historically, patients with melanoma brain metastases survive four to five months, on average.

“About half of advanced melanoma patients will develop brain metastases,” Ahmed says. “Improving outcomes in these metastatic melanoma patients who have the worst prognosis is very important.”

In the study, all brain metastases were treated with stereotactic radiosurgery (SRS) in a single session except for 12, who were treated with fractionated stereotactic radiation therapy, nine of whom were in the postoperative setting.

One patient experienced grade 2 headaches following SRS with symptomatic relief with steroid treatment. No other treatment-related neurologic toxicities or scalp reactions were reported.

Eight local brain metastases (11 percent) failures with a greater than 20 percent increase in volume were noted in the study. Of these lesions, hemorrhage was noted in four and edema was noted in seven.

“We found [Opdivo] combined with either radiation treatment before, during, or after was very well tolerated,” said Ahmed. “There were no neurotoxicity or cutaneous side effects, which we would not expect with radiation treatment alone. We know the two agents can be combined safely based on this study.”The current standard of care for melanoma brain metastasis is focal radiation treatment for patients with limited disease, and whole brain radiation for patients with advanced disease. As Opdivo and other immunotherapies become more commonly used in melanoma, it is important to understand how they will work in conjunction with radiation, says Ahmed.

Treating brain metastases requires a multidisciplinary approach, especially in melanoma. Cutaneous oncologists, radiation oncologists, and neurosurgeons, he adds, need to work together to determine optimal treatment plans.

“Multiple systemic agents have proven to have a survival benefit in advanced melanoma, and it is important to see how these therapies interact with radiation treatment as well as surgery,” Ahmed says. “What we’ve seen here at Moffitt is that immunotherapy and radiation treatment can be safely combined, with improved local and distant brain control as well as overall survival in patients with brain metastases.”

Following this retrospective analysis, there are plans to evaluate Opdivo and radiation therapy in the prospective setting to better understand the potential synergistic effects between the two.

“A lot of work needs to be done to see how we can improve outcomes in the management of melanoma brain metastases, but what we’ve learned here is a good start,” Ahmed says.

Opdivo is currently FDA approved to treat non—small cell lung cancer, renal cell carcinoma and melanoma.

Ahmed KA, Stallworth DG, Kim Y, et al. Clinical outcomes of melanoma brain metastases treated with stereotactic radiation and anti-PD-1 therapy [published online December 27, 2015]. Ann Oncol. doi:10.1093/annonc/mdv622.