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Article / Publication Details
Abstract
Introduction
Checkpoint inhibitors (CPI) have significantly improved survival among patients with various cancer types. Prior studies have shown a correlation between immune cell infiltration and poorly differentiated cancers. This study evaluated the impact of poorly differentiated histology on survival in patients with advanced gastrointestinal cancers treated with immunotherapy.
Methods
This study was a retrospective, single-center analysis of patients with gastrointestinal cancers treated with checkpoint inhibitors between 2016 and 2021. Univariate (UVA) and multivariable analyses (MVA) were performed to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to assess the association between tumor and patient characteristics, progression free survival, and overall survival.
Results
A total of 123 patients were eligible and included in the analysis. Median age was 66 years (23-88 years). Majority had stage IV disease (89%), were white (65.5%), and were male (64.5%). Most common diagnoses were hepatocellular carcinoma (30.5%), gastric adenocarcinoma (16.5%) ,esophageal adenocarcinoma (17%) and colorectal cancer (19.8%). About 32% of the tumors were microsatellite instability-high (MSI-HIGH/DMMR), with BRAF V600E mutation rate of 10%. About 25% of the patients received checkpoint inhibitors as initial treatment while 35.5% had received two or more prior lines of therapy. Compared with well and moderately differentiated histology, patients with poorly differentiated tumors had a shorter median overall survival (mOS) (not reached [NR] vs. NR vs. 9.3 months, p=0.0264). There was no statistically significant difference in median progression free survival between histology types (2.5 vs.4.2 vs. 2 months, p=0.1314). On univariate survival analysis, moderately differentiated tumors correlated with a significantly longer mOS (HR: 0.48, CI: 0.24-0.93, p=0.030) and mPFS (HR: 0.62, 95%CI: 0.38-1.00, p=0.048) compared to poorly differentiated histology. Female patients (HR: 0.55, 95%CI: 0.34-0.90, p=0.018) and Eastern Cooperative Oncology Group (ECOG) of 1 (vs. ≥2) had significantly longer mPFS (HR: 0.58, 95%CI: 0.35-0.97, p=0.036). ECOG of 1 also correlated with longer mOS (HR: 0.47, 95%CI: 0.23-0.94, p=0.034). Microsatellite stable (MSS) tumors had significantly shorter mPFS (HR: 5.74, 95%CI: 2.41-13.63, p
S. Karger AG, Basel
Article / Publication Details
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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