In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e22041-e22041
Abstract:
e22041 Background: Pembrolizumab (PEMBRO) improves survival in advanced melanoma (MEL). This research investigates baseline (BL) biomarkers that predict long-term benefit on PEMBRO monotherapy. Methods: Outcome data on patients (pts) with advanced cutaneous/mucosal MEL treated with PEMBRO in our institution were collected after pt consent. Responses were evaluated using the immune-related response criteria. Total metabolic tumor volume (TMTV), assessed by 18-fluorodeoxyglucose positron emission tomography/computed tomography, was calculated as the sum of all tumor-associated voxels with a standardized uptake value (SUV) above the mean SUV measured in a reference region in normal liver tissue plus 3 standard deviations using Syngo.via software (Siemens Healthcare). The NanoString PanCancer IO360 panel was used for gene expression profiling (GEP). Results: A total of 196 pts was included in this analysis (median age 60; cutaneous 86%, mucosal 3%, unknown primary 12%; stage III 14%, IV-M1a/b/c 60%, IV-M1d 26%; first-line 24%). Median progression-free survival (PFS) in the population was 20.4 w (95% CI 10.2-30.7); median overall survival (OS) was 143.6 w (95% CI NR-NR). BL WHO Performance Status (PS) 〉 0 (HR 1.63 [95% CI 1.13-2.37]), C-reactive protein (CRP) 〉 ULN (HR 1.92 [95% CI 1.33-2.77]), absolute lymphocyte count (ALC) 〈 750/mm³ (HR 2.45 [95% CI 1.32-4.55]) and 〉 1 metastatic site (HR 1.84 [95% CI 1.23-2.77]) were associated (P≤0.01) with worse PFS in multivariate analysis (Cox regression); BL WHO PS 〉 0 (HR 2.77 [95% CI 1.82-4.24]), lactate dehydrogenase (LDH) 〉 ULN (HR 1.80 [95% CI 1.16-2.79]) and 〉 1 metastatic site (HR 1.95 [95% CI 1.16-3.25]) were associated with worse OS (P≤0.011). BL TMTV data were available in 118 pts (60%): BL CRP 〉 ULN (HR 1.83 [95% CI 1.13-2.96]), ALC 〈 750/mm³ (HR 2.49 [95% CI 1.02-6.08]), 〉 1 metastatic site (HR 1.71 [95% CI 1.04-2.82]) and BL corticosteroid use (HR 4.62 [95% CI 1.38-15.45] ) were associated with worse PFS (P 〈 0.05). BL WHO PS 〉 0 (HR 2.82 [95% CI 1.57-5.08]), ALC 〈 750/mm³ (HR 2.62 [95% CI 1.06-6.51]), history of brain metastases (HR 2.59 [95% CI 1.37-4.91] ) and TMTV 〉 80 mL (HR 3.56 [95% CI 1.82-6.95]) were all associated with worse OS (P≤0.038). GEP data on a representative BL tumor sample were available in 27 pts (14%). Higher apoptosis signature scores were associated with increased probability of OS (HR 0.45 [95% CI 0.33-0.73] , P 〈 0.01). Conclusions: BL TMTV 〉 80 mL identifies a subgroup of advanced MEL pts with worse outcome on PEMBRO. Increased apoptosis gene signature scores in a subset of patients predict increased OS.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2020.38.15_suppl.e22041
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2020
detail.hit.zdb_id:
2005181-5
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