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Found 1 Presentation For Request "117P"
117P - Tumour mutation burden and response to immune checkpoint inhibitors in solid tumors: A systematic review and meta-analysis
- Khalil Choucair (Wichita, United States of America)
Abstract
Background
Immune Checkpoint Inhibitors (ICIs) have revolutionized therapies in various solid tumors. Despite, promising and durable response rates compared to non-immune therapies, not all patients respond as effectively to ICIs. There is thus a strong need to explore biomarkers of response that can contribute to proper patient selection and potentially expand indications of ICIs beyond the current, histology-defined populations. Tumor mutation burden (TMB) is an emerging genomic biomarker that quantifies the total number of neo-antigens present in a tumor specimen. Therefore, a systematic review and meta-analysis were conducted to explore the association between TMB and outcomes of ICIs across several solid tumors.
Methods
PubMed, Embase, Web of Science, and Cochrane databases (up to December 2019) were searched for eligible studies involving patients with solid tumors who received ICIs, and with clearly defined TMB cut-off values. Studies reporting 1-year overall survival (1-YR OS), median progression-free survival (mPFS), and median overall survival (mOS) were included in the qualitative analysis. The primary endpoint of the meta-analysis was 1-YR OS and the pooled hazard ratios (HR) and 95% confidence interval (CI) for 1-YR OS were performed using random effect model.
Results
A total of 17 studies including 3,938 patients met eligibility criteria: the majority of patients had non-small cell lung carcinoma (n=1,481). Patients received ICIs as 1st line therapy (n=1,081), or > 1st line (n=1,421). The line of therapy was not reported in all studies. Nine studies involved PD-1/PD-L1 monotherapy, one involved CTLA-4, four involved a combination of both, and three involved various ICIs. In the meta-analysis, a total of 2,156 patients from 10 studies reporting 1-YR OS were included. Comparing high (n=631) to low TMB (n=1,525), the pooled HR for 1-YR OS was -0.81 [95% CI: -1.63 to 0.02; P < 0.01] in patients with high TMB.
Conclusions
TMB may be a tumor-agnostic biomarker of response to ICIs and survival. Further sub-group analysis by TMB cut-off levels, ICIs and lines of therapy is warranted. Future research ought to focus on harmonization of sequencing and reporting methodologies.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.