Safety and activity of combined radiation therapy (RT) and anti-PD-1 antibodies (PD-1) in patients (pts) with metastatic melanoma

Purpose/Objective(s):
Prior studies have suggested that RT can induce an abscopal immune response that may be enhanced with the addition of immunotherapy such as ipilimumab. This effect is thought to be driven via the release of tumor antigens and subsequent immune recognition. We sought to review the clinical outcomes of patients receiving RT immediately prior to or during PD-1 therapy.

Materials/Methods:
All patients receiving pembrolizumab or nivolumab for unresectable stage III/IV melanoma who had sequential (within 4 weeks prior to PD-1 commencement) or concurrent RT were identified. Details of RT treatment, systemic treatment, clinical outcome and toxicity were collected.

Results:
Of 170 pts treated with a PD-1 antibody at two centers, 36 had either sequential RT (n=10, 28%), concurrent RT (n=23, 65%), or both (n=3, 8%). 29 pts received pembrolizumab and 7 received nivolumab. 31 (86%) pts received prior ipilimumab (median number doses 2.9). 24 pts had RT to extracranial sites, 3 had stereotactic RT (SRS) to brain metastases and 4 had whole brain RT (WBRT). 5 pts had a combination of these. 13 pts had RT to a metastasis progressing on PD-1. No excess RT toxicities were observed, except radionecrosis in one patient and potential delayed neurotoxicity in a single patient with multiple small asymptomatic brain metastases treated with a single dose of ipilimumab closely followed by pembrolizumab with concurrent WBRT (20Gy/5#). 16 patients had brain metastases at start of PD-1 therapy (median number of brain metastases 4). Of the 12 patients that underwent SRS/WBRT to brain metastases, after median follow-up of 17.2 weeks (range 2.1-30.9) 3 have died and median overall survival has not been reached. Irradiated and non-irradiated lesion-specific and site-specific (intracranial and extracranial) response rates and progression-free survival will be examined, and updated survival analyses will be performed.

Conclusion:
These results suggest that RT and PD-1 can be safely administered sequentially or concurrently with no excess acute toxicity. The potential for delayed toxicity with cerebral RT requires further investigation. Patients with brain metastases treated with cerebral RT and PD-1 may have superior survival compared to historical data. Further analyses with more mature follow-up will be presented.