Sites of metastasis and association with clinical outcome in advanced stage cancer patients treated with immunotherapy.

• Type of Material: Article
• Authors: Mehmet Bilen, Emory University; Julie M. Shabto, Emory University; Dylan J. Martini, Emory University; Yuan Liu, Emory University; Colleen Lewis, Emory University; Hannah Collins, Emory University; Mehmet Akce, Emory University; Haydn Thomas Kissick, Emory University; Bradley Carthon, Emory University; Walid Shaib, Emory University; Olatunji Alese, Emory University; Conor Ermst Steuer, Emory University; Christina Wu, Emory University; David H Lawson, Emory University; Ragini R. Kudchadkar, Emory University; Viraj Master, Emory University; Bassel El-Rayes, Emory University; Suresh Ramalingam, Emory University; Taofeek K Owonikoko, Emory University; R Donald Harvey, Emory University
• Language: English
• Date: 2019-08-29
• Publisher: BMC (part of Springer Nature)
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s). 2019
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s12885-019-6073-7
• Title of Journal or Parent Work: BMC Cancer
• ISSN: 1471-2407
• Volume: 19
• Issue: 1
• Start Page: 857
• End Page: 857
• Grant/Funding Information: Research reported in this publication was supported in part by the Biostatistics and Bioinformatics Shared Resource of the Winship Cancer Institute of Emory University and NIH/NCI under award number P30CA138292.
• Keywords: Sites of metastasis; Tumor immunology; Tumor microenvironment; Immunotherapy; Immune checkpoint blockade; Clinical outcomes; Phase 1 clinical trials; Liver metastasis
• Research Categories: Health Sciences, Oncology; Health Sciences, Immunology

Abstract

BACKGROUND: Selecting the appropriate patients to receive immunotherapy (IO) remains a challenge due to the lack of optimal biomarkers. The presence of liver metastases has been implicated as a poor prognostic factor in patients with metastatic cancer. We investigated the association between sites of metastatic disease and clinical outcomes in patients receiving IO. METHODS: We conducted a retrospective review of 90 patients treated on IO-based phase 1 clinical trials at Winship Cancer Institute of Emory University between 2009 and 2017. Overall survival (OS) and progression-free survival (PFS) were measured from the first dose of IO to date of death or hospice referral and clinical or radiographic progression, respectively. Clinical benefit (CB) was defined as a best response of complete response (CR), partial response (PR), or stable disease (SD). Univariate analysis (UVA) and Multivariate analysis (MVA) were carried out using Cox proportional hazard model or logistic regression model. Covariates included age, whether IO is indicated for the patient's histology, ECOG performance status, Royal Marsden Hospital (RMH) risk group, number of metastatic sites, and histology. RESULTS: The median age was 63 years and 53% of patients were men. The most common histologies were melanoma (33%) and gastrointestinal cancers (22%). Most patients (73.3%) had more than one site of distant metastasis. Sites of metastasis collected were lymph node (n = 58), liver (n = 40), lung (n = 37), bone (n = 24), and brain (n = 8). Most patients (80.7%) were RMH good risk. Most patients (n = 62) had received 2+ prior lines of systemic treatment before receiving IO on trial; 27 patients (30.0%) received prior ICB. Liver metastases were associated with significantly shorter OS (HR: 0.38, CI: 0.17-0.84, p = 0.017). Patients with liver metastasis also trended towards having shorter PFS (HR: 0.70, CI: 0.41-1.19, p = 0.188). The median OS was substantially longer for patients without liver metastases (21.9 vs. 8.1 months, p = 0.0048). CONCLUSIONS: Liver metastases may be a poor prognostic factor in patients receiving IO on phase 1 clinical trials. The presence of liver metastases may warrant consideration in updated prognostic models if these findings are validated in a larger prospective cohort.