Immunotherapy extends OS in melanoma with brain metastases
The FDA approval and subsequent use of checkpoint blockade immunotherapy (CBI) and BRAFV600 targeted therapy almost doubled the overall survival (OS) in patients with stage 4 melanoma with brain metastases (MBM), according to a recent US-based study.
“[W]e observed a 91 percent relative increase in the 4-year OS rate of MBM patients compared with those MBM patients who were diagnosed prior to 2011,” said the researchers.
“The results of our analyses indicate that immune checkpoint inhibitors can achieve a meaningful therapeutic benefit for metastatic melanoma, including spread to the central nervous system [CNS],” said study author Professor David Reardon from the Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, US.
Four-year OS in patients with MDM rose from 7.4 percent to 14.1 percent after the FDA approved the use of CBI and BRAFV600 targeted therapies in 2011, reflecting a relative increase of 91 percent (p<0.001), with median OS increasing from 5.1 to 6.2 months (p<0.001). [Cancer Immunol Res 2018;doi:10.1158/2326-6066.CIR-18-0067]
The receipt of CBI in the first-line setting increased threefold, from 10.5 percent of patients with MBM receiving CBI in 2011 to 34.0 percent in 2015 (p<0.001). Compared with patients with MBM who did not receive CBI, patients who received first-line CBI had longer median OS (12.4 vs 5.2 months; p<0.001) as well as a higher 4-year OS rate (28.1 percent vs 11.1 percent; p<0.001), with the findings particularly pronounced among patients with MBM but without extracranial metastases (56.4 vs 7.7 months; p<0.001 and 51.5 percent vs 16.9 percent, respectively).
Patients who received both CBI and BRAFV600 targeted therapy (n=59) demonstrated a trend toward improved OS compared with those who received CBI only (median, 10.5 vs 7.8 months; p=0.05).
The findings were based on data obtained from the US-based National Cancer Database which researchers used to identify 2,753 patients aged >20 years who were newly diagnosed with stage 4 cutaneous MBM between 2010 and 2015. Of these, 60.3 percent (n=1,660) were diagnosed with MBM and extracranial metastatic disease, a majority of whom had lung involvement (82.9 percent).
The median OS without treatment was 1.8 months in patients with MBM, with a 1-year OS rate of 12.4 percent.
While most cases of melanoma are diagnosed early and thus successfully treated with surgery, patients with advanced melanoma do not respond well to conventional therapy, resulting in poor OS of less than 1 year, said the researchers.
“Historically, CNS metastases from melanoma as well as other solid tumour types have proven particularly challenging to treat, with most therapeutic approaches providing minimal clinical benefit for patients,” said Reardon. “At the same time, not all patients benefit, indicating that much research is still required to optimize the potential of anti-tumour immune responses for CNS metastatic disease,” he said.
“Through the use of nationwide cancer data, for the first time we can evaluate the impacts on survival that these exciting new therapies have for patients with melanoma brain metastases,” added senior author Assistant Professor Timothy Smith from Brigham and Women’s Hospital/Harvard Medical School, Boston, Massachusetts, US.
Nonetheless, the Database only provides OS data and as such, the researchers could not account for the impact of CBI on progression- or recurrence-free survival. The Database also did not provide information on BRAF mutational status, with the receipt of BRAFV600 targeted therapy being used as a “proxy” for mutational status.
“Our findings build on the revolutionary success of CBI clinical trials for advanced melanoma and demonstrate that their substantial survival benefits also extend to melanoma patients with brain metastases,” said corresponding author Dr J. Bryan Iorgulescu, also from Brigham and Women’s Hospital/Harvard Medical School.