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MO_8_2644 - The use of anti-PD1 therapy in melanoma patients with known brain metastases: Survival, durable intracranial progression free survival and radionecrosis

Monday, October 22
10:45 AM - 12:15 PM
Location: Innovation Hub, Exhibit Hall 3

The use of anti-PD1 therapy in melanoma patients with known brain metastases: Survival, durable intracranial progression free survival and radionecrosis
R. Rahman1, A. Niemierko2, A. Cortes3, K. S. Oh2, K. T. Flaherty2, D. P. Lawrence2, R. J. Sullivan2, and H. A. Shih4; 1Harvard Radiation Oncology Program, Boston, MA, 2Massachusetts General Hospital, Boston, MA, 3Hospital Universitario Ramon y Cajal, Madrid, Spain, 4Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA

Purpose/Objective(s): Patients with brain metastases from melanoma historically have a poor prognosis. In addition to radiation therapy and surgery, immunotherapy agents including anti-PD1 therapy have known intracranial activity. This study sought to evaluate outcomes and predictors of intracranial progression free survival (PFS) and overall survival (OS) of melanoma patients with brain metastases treated with anti-PD1 therapy.

Materials/Methods: We retrospectively reviewed a single institution’s experience of consecutive melanoma patients receiving an anti-PD1 agent between 2012-2016 who received intracranial radiation during their disease course. Patients were required to have pre-treatment and post-treatment MRIs. Patient, treatment and imaging data were reviewed. Untreated disease was defined as evidence of intracranial disease that did not receive surgery or radiation as of 30 days after initiating anti-PD1 therapy. CNS progression was defined as new enhancing lesion or >20% increase in sum of one-dimensional measurements of lesions. Intracranial PFS and OS were measured from time of anti-PD1 initiation, and data was analyzed using Kaplan-Meier survival analysis and Cox proportional hazards modeling.

Results: We identified 49 melanoma patients with known brain metastases. Median age was 66 (range 21-88). Among these patients, 36 (73%) had received prior intracranial RT, 17 (35%) had underwent intracranial surgery, and 14 of 21 (66%) BRAF mutant patients had received a BRAF-targeted therapy. Anti-PD1 therapy included pembrolizumab (69%), nivolumab (27%), or an investigational agent (4%). At time of anti-PD1 initiation, 41 (84%) patients had ECOG performance status 0-1, 47 (96%) had extracranial disease, and 11 (22%) had untreated intracranial disease. Median OS was 24.8 months, and OS at 1 and 2 years were 63.3% and 51.7%, respectively. Median intracranial PFS was 11.6 months, and intracranial PFS at 1 and 2 years were 48.0% and 39.3%, respectively. On multivariable analysis, ECOG performance status ≥ 2 (AHR 4.17, p=0.010) and untreated intracranial disease (AHR 3.61, p<0.001) were associated with worse PFS, while ECOG performance status ≥2 (AHR 3.40, p=0.027) and known BRAF mutation (AHR 3.42, p=0.009) were associated with worse OS. With respect to toxicity, 4 patients (9%) developed symptomatic radionecrosis.

Conclusion: A notable proportion of melanoma patients with brain metastases can attain durable intracranial control and long-term survival in the era of anti-PD1 therapy. Untreated intracranial disease was associated with worse outcomes, suggestive of a benefit of aggressive local therapy for patients to be managed with anti-PD1 therapy. Patients with a BRAF mutation, many of whom had been previously treated with targeted inhibitors, had a worse OS compared to BRAF wild-type patients in our cohort. Prospective trials are necessary to validate our findings.

Author Disclosure: R. Rahman: None. A. Niemierko: None. K.S. Oh: Research Grant; Merck & Co., Inc, Elekta. CME editor; IJROBP. K.T. Flaherty: Consultant; Merck, BMS, Genentech. D.P. Lawrence: None. R.J. Sullivan: Consultant; Novartis, Merck. H.A. Shih: Employee; Dartmouth Hitchcock. Honoraria; UpToDate. Chief, CNS & Eye Radiat Oncol Services; Massachusetts General Hospital. Associate Medical Director; MGH Proton Therapy Center. Associate Director; Harvard Radiation Oncology Program.

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