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Prognostic factors for overall survival (OS) in metastatic melanoma (MM) patients (pts) treated with immune checkpoint inhibitors: A single institution study of 696 pts

Authors :
Lauren E. Haydu
Patrick Hwu
Michael K. Wong
Michael A. Davies
Meredith Ann McKean
Jennifer L. McQuade
Roland L. Bassett
Hussein Abdul-Hassan Tawbi
Sapna Pradyuman Patel
Adi Diab
Rodabe N. Amaria
Isabella C. Glitza
Wen-Jen Hwu
Junsheng Ma
Source :
Journal of Clinical Oncology. 35:9574-9574
Publication Year :
2017
Publisher :
American Society of Clinical Oncology (ASCO), 2017.

Abstract

9574 Background: Limited OS data, including prognostic and predictive factors of response, is available in mm pts treated with immune checkpoint inhibitors. Methods: A single-institution retrospective review was conducted on 696 mm pts treated with single-agent anti CTLA-4 or anti PD-1 on and off clinical trial between 2011-2015. Median OS was calculated from mm diagnosis. Results:Median age at mm diagnosis was 60 years old (range 15-86) and 65.2% were male. Subtypes were 63.2% non-acral cutaneous, 17.2% unknown primary, 7.8% mucosal, 6.5% acral, and 5.3% uveal. AJCC v7 staging at diagnosis was 7.9% M1a, 16.5% M1b, 33.0% M1c, and 42.5% not staged due to unknown LDH. LDH was elevated in 18.0% (400 pts). Mutation rates were 30.0% BRAF V600E/K (636 pts tested) and 24.5% NRAS (429 pts tested). First-line therapy for BRAF V600E/K mm pts included anti CTLA-4 (24.1%), BRAF/MEK targeted therapy (21.5%) and anti PD-1 (8.9%). First-line therapy for BRAF WT mm pts included anti CTLA-4 (28.1%) and anti PD-1 (12.8%). Median OS from mm for the cohort was 36.5 months (95% CI 33.3-44.9). Elevated LDH and staging correlated with OS (p < 0.001, p < 0.001, respectively) on univariate analysis. Age, gender, subtype and mutation status were not significantly associated with OS. Compared to BRAF WT, pts with BRAF V600E/K mutation were younger (median = 53 vs 62 yrs, p < 0.001), more likely to have non-acral cutaneous mm (83.2% vs 58.0%, p < 0.001) and have a diagnosis of brain metastasis during the disease course (57.0% vs 28.8%, p < 0.001). While adjusting for stage, there was no significant difference in OS based on first or second line therapy in pts with BRAF V600E/K mm or first line therapy in BRAF WT MM; however, BRAF WT pts treated second line with anti-PD1 were observed to have improved OS compared with pts receiving anti-CTLA 4 (HR 0.43 95% CI:0.23-0.84 p = 0.012). Conclusions: This study demonstrates that LDH and stage are prognostic of OS in all mm pts treated with single agent immune therapy. Second line therapy in BRAF WT pts treated with single agent immune therapy is also prognostic of OS thus prompting further investigation to determine advantageous therapy sequencing in MM.

Details

ISSN :
15277755 and 0732183X
Volume :
35
Database :
OpenAIRE
Journal :
Journal of Clinical Oncology
Accession number :
edsair.doi...........1d6be92d2fba5ae9dfcb37be62505d3b