Baseline total metabolic tumor volume assessed by 18FDG-PET/CT predicts outcome in advanced melanoma patients treated with pembrolizumab

Research output: Unpublished contribution to conferencePoster

Abstract

BACKGROUND Pembrolizumab (PEMBRO) improves survival in patients (pts) with advanced melanoma (MEL). Baseline (BL) parameters that predict long-term benefit for PEMBRO treatment are under investigation. METHODS Outcome data of pts with advanced MEL treated with PEMBRO at our institution were collected as part of a prospective therapeutically non-interventional trial. Objective responses were evaluated using the immune-related response criteria. Total metabolic tumor volume (TMTV) was assessed by 18-fluorodeoxyglucose positron emission tomography (18FDG-PET/CT) using MIM Encore Software®. TMTV was defined as the sum of all tumor-associated voxels with a standardized uptake value (SUV) higher than the mean SUV measured in a reference region in normal liver tissue + 3 standard deviations. RESULTS BL 18FDG-PET/CT disease staging results were available for 69 pts. Median progression-free survival (mPFS) was 19 w (95% CI 9-29); median overall survival (mOS) was 130 w. A cut-off value of 90 mL of BL TMTV defined a subpopulation with significantly worse PFS (mPFS 7 w [95% CI 4-9] vs 56 w [95% CI 0-118]; HR 19.10, p<0.001) and OS (mOS 21 w [95% CI 2-41] vs not reached; HR 46.14, p<0.001). Additionally, a history of brain metastases (HBM), C-reactive protein (CRP) >5 times upper limit of normal (>5xULN), lactate dehydrogenase (LDH) >1xULN, WHO Performance Status (WHO PS) ≥1 and number of metastatic sites ≥2 were associated with significantly shorter PFS and OS in univariate analysis (log rank p<0.05). In multivariate analysis (Cox multivariate logistic regression), a BL TMTV >90 mL (HR 3.70 [95% CI 1.79-7.69]), HBM (HR 2.08 [95% CI 1.11-3.85]) and WHO PS ≥1 (HR 2.08 [95% CI 1.12-3.85]) were significantly associated with shorter PFS; BL TMTV >90 mL (HR 14.29 [95% CI 5.26-33.33]) and HBM (HR 2.56 [95% CI 1.23-5.26]) were significantly associated with shorter OS. CONCLUSIONS BL TMTV >90 mL and HBM independently correlate with worse PFS and OS in pts with advanced MEL treated with PEMBRO. Elevated BL CRP and LDH values overlap with, but are inferior to TMTV as predictive biomarkers for outcome of PEMBRO treatment. Confirmation of these results is under investigation in an independent second cohort.
Original languageEnglish
Publication statusPublished - 13 Dec 2018
EventESMO Immuno-Oncology Congress 2018 - Geneva, Switzerland
Duration: 13 Dec 201816 Dec 2018
https://www.esmo.org/Conferences/ESMO-Immuno-Oncology-Congress-2018/Abstracts

Conference

ConferenceESMO Immuno-Oncology Congress 2018
CountrySwitzerland
CityGeneva
Period13/12/1816/12/18
Internet address

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