title: A Retrospective Analysis of the Efficacy of Pembrolizumab in Melanoma Patients With Brain Metastasis.
abstract: A total of 50% of patients with melanoma will develop brain metastasis (BM). Pembrolizumab was approved for treatment of metastatic melanoma on the basis of significant systemic antitumor activity. Because of low enrollment of patients with BM in pembrolizumab trials, efficacy against melanoma BM remains unknown. We reviewed records of 89 consecutive patients with melanoma treated with pembrolizumab at our institution between May 1, 2014 and October 31, 2015 to determine the time to progression. Thirty-six (40%) patients had BM before pembrolizumab. Twenty-six (72%) patients with BM had received prior treatment for BM. With median follow-up of 17.2 months, 54 patients (61%) developed progressive disease on pembrolizumab. Intracranial progression occurred in 19 patients (21%), 3 of whom did not have BM before treatment. Median time to progression at any site was 6 months for those without BM (n=53), 5 months for those with treated BM (n=26), and 1.2 months for patients with untreated BM (n=10). Using a Cox regression model adjusted for baseline factors, there was a statistically significant (Wald χ P=0.003) reduction in the hazard of progression for patients without BM [hazard ratio, 0.19; 90% confidence interval, 0.08-0.42) and patients with treated BM (hazard ratio, 0.27; 90% confidence interval, 0.12-0.64) compared with those with untreated BM. In conclusion, melanoma patients with pretreated BM can have durable systemic responses to pembrolizumab. Large, prospective studies are needed to evaluate the intracranial antitumor activity of pembrolizumab in melanoma patients with untreated BM.
authors.affiliation: *Massachusetts General Hospital Cancer Center †Department of Radiology, Massachusetts General Hospital, Harvard Medical School ‡Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Ibiayi
authors.initials: I
authors.lastname: Dagogo-Jack
authors.forename: Michael
authors.initials: M
authors.lastname: Lanfranchi
authors.forename: Justin F
authors.initials: JF
authors.lastname: Gainor
authors.forename: Anita
authors.initials: A
authors.lastname: Giobbie-Hurder
authors.forename: Donald P
authors.initials: DP
authors.lastname: Lawrence
authors.forename: Alice T
authors.initials: AT
authors.lastname: Shaw
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Sullivan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000074322:Antineoplastic Agents, Immunological; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000556:secondary; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000074322:Antineoplastic Agents, Immunological; C582435:pembrolizumab