FDG-PET response and outcome from anti-PD-1 therapy in metastatic melanoma

Abstract

Background

Immune checkpoint inhibitor therapy has resulted in impressive and durable clinical activity for many cancers including melanoma, however there remain few reliable predictors for long-term response. This study investigated whether FDG-PET imaging may better predict long-term outcomes compared to standard CT response criteria.

Patients and methods

Retrospective analysis of metastatic melanoma patients treated with anti-PD-1 based immunotherapy with baseline and 1-year ¹⁸F-FDG PET and CT imaging at Melanoma Institute Australia. 1-year response was determined using RECIST for CT and EORTC criteria for PET, coded as complete response (CR or CMR), partial response (PR or PMR), stable disease (SD or SMD) or progressive disease (PD or PMD). Progression-free survival (PFS) was determined from the 1-year landmark.

Results

104 patients were evaluated with median follow-up 30.1 months and 98% remain alive. Most received anti-PD-1 as monotherapy (67%) or combined with ipilimumab (31%). At 1-year, 28% had CR, 66% had PR and 6% had SD on CT, while 75% had CMR, 16% PMR and 9% SMD/PMD on PET. CMR was observed in 68% of patients with PR on CT. RECIST PFS post 1-year landmark was similar in patients with CR vs PR/SD, but improved in patients with CMR vs non-CMR (median not reached [NR] vs 12.8 mths; HR 0.06 [95% CI 0.02-0.23]; p<0.01). In patients with PR on CT, PFS was improved in patients with PR+CMR vs PR+non-CMR (median NR vs 12.8 months; HR 0.07 [95% CI 0.02-0.27]; p<0.01). In the 78 CMR patients, 78% had discontinued treatment and 96% had ongoing response.

Conclusions

Whilst only a small proportion of patients have a CR at 1-year, most patients with a PR have CMR on PET. Almost all patients with CMR at 1-year have ongoing response to therapy thereafter. PET may have utility in predicting long-term benefit and help guide discontinuation of therapy.