The Mayo Clinic experience in patients with metastatic melanoma who have failed previous pembrolizumab treatment.

Abstract

e21014 Background: Blockade of programmed death (PD-1) receptor has shown unprecedented rates of durable clinical responses in patients with metastatic melanoma. However, the majority of patients eventually progress on anti-PD-1 therapy. Currently, there is no standard strategy guiding the treatment in this setting, partly due to the lack of knowledge of the clinical course after PD-1 blockade failure. Methods: We retrospectively reviewed 140 patients with metastatic melanoma treated with pembrolizumab at Mayo Clinic, Rochester, between January 1, 2012 and November 1, 2015, identifying 70 patients who failed pembrolizumab treatment (due to disease progression or toxicity). The clinical outcomes and RECIST objective response rates (ORR) to treatments received after pembrolizumab were assessed. Results: Of the 70 patients who failed pembrolizumab therapy, 48 received further systemic therapies. Of these, 43 had complete follow-up data and were included in our analysis. Thirty patients received 1 line of subsequent therapy; while 13 patients received multiple subsequent treatments (average 2.5). Eighteen patients with a BRAF mutation received targeted therapy, 9 of whom received targeted therapy alone, with an ORR of 55.6% and 0% stable disease (SD). Nine of these 18 BRAF mutant patients received targeted therapy combined with chemotherapy and/or immunotherapy, with an ORR of 22.2% and 33.3% SD. Twenty two of the 43 patients received immunotherapy (nivolumab and/or ipilimumab or pembrolizumab)-based treatment (alone or in combination with chemotherapy), with an ORR of 31.8%, and 13.6% SD. Nineteen of the 43 patients received chemotherapy alone with an ORR of 26.3% and 0% SD. Conclusions: Patients with metastatic melanoma who failed previous pembrolizumab therapy appear to benefit from further systemic treatments, including additional immunotherapy. Combination therapies show favorable clinical outcomes. The biological mechanism of combining PD-1 blockade with other therapy modalities is currently being studied and will further improve patient outcomes.