Dataset Information

High tumor mutation burden predicts better efficacy of immunotherapy: a pooled analysis of 103078 cancer patients.

ABSTRACT: The relation between tumor mutation burden (TMB) and outcome of cancer patients receiving immunotherapy has been reported. This study aimed to evaluate the prognostic role of TMB in cancer patients receiving immunotherapy. Databases including Embase, PubMed, and the Cochrane library were systematically searched to identify potentially eligible studies until Sep 2018 without language limitation. Studies assessing high versus low TMB in predicting survival of various cancer patients were selected. The pooled analyses were conducted using hazard ratio (HR) of high versus low TMB for overall survival (OS) and progression-free survival (PFS), and the odds ratio (OR) for overall response rate (ORR). The primary endpoint was OS. Secondary outcomes were PFS and ORR. A total of 45 studies consisting of 103078 cancer patients were included. The combined results showed that high TMB was associated with better OS (HR = 0.40; 95% confidence interval (CI):0.30-0.53; p< .00001), PFS (HR = 0.37; 95% CI: 0.26-0.53; p< .00001) and ORR (OR = 4.62; 95%CI: 2.90-7.34; p< .0001) when treated with immunotherapy. In studying patients with high TMB, these patients had improved OS (HR = 0.69; 95%CI: 0.47-1.03; p= .07) when comparing immunotherapy to chemotherapy. Subgroup analyses suggested that the prognostic role of TMB was independent of cancer types and TMB detection methods (all p< .05). Our findings suggest that high TMB is associated with better survival in cancer patients receiving immunotherapy. For cancer patients with high TMB, immunotherapy could be considered.

SUBMITTER: Cao D

PROVIDER: S-EPMC6685508 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

High tumor mutation burden predicts better efficacy of immunotherapy: a pooled analysis of 103078 cancer patients.

Cao Dedong D Xu Huilin H Xu Ximing X Guo Tao T Ge Wei W

Oncoimmunology 20190616 9

The relation between tumor mutation burden (TMB) and outcome of cancer patients receiving immunotherapy has been reported. This study aimed to evaluate the prognostic role of TMB in cancer patients receiving immunotherapy. Databases including Embase, PubMed, and the Cochrane library were systematically searched to identify potentially eligible studies until Sep 2018 without language limitation. Studies assessing high versus low TMB in predicting survival of various cancer patients were selected. ...[more]

PMID: 31428527

Similar Datasets

Project description:Objective: Panel-based sequencing is widely used to measure tumor mutational burden (TMB) in clinical trials and is ready to enter routine diagnostics. However, cut-off points to distinguish "TMB-high" from "TMB-low" tumors are not consistent and the clinical implications of TMB in predicting responses to immune checkpoint blockade (ICB) in gastric cancer are not clearly defined. We aimed to assess whether TMB is associated with the response to immunotherapy and to examine its relation with other biomarkers of immunotherapy response in advanced gastric cancer. Design: In total, 63 patients with advanced gastric cancer treated with ICB were included in the study. Panel-based TMB in gastric tumor samples, treatment responses to ICB, clinicopathological data, and time to progression were retrospectively analyzed. Microsatellite instability (MSI) status, Epstein-Barr virus (EBV) positivity, and programmed death-ligand 1 (PD-L1) combined positive score (CPS) were also analyzed. Results: TMB ranged from 0 to 446 mutations/megabase (mt/mb) and was significantly associated with MSI (P < 0.001), PD-L1 CPS (P = 0.022), response to ICB (P = 0.04), chemotherapy (P = 0.02) and older patient age (?65 years; P = 0.0014). The cut-off point of 14.31 mt/mb determined by log-rank statistics for progression-free survival divided the tumors into eight (12.7%) TMB-high and 55 (87.3%) TMB-low tumors. The median TMB of the chemo-refractory group was significantly higher (8.43 mt/mb) compared to that of chemo-naïve group (3.42 mt/mb) (P = 0.02). Patients with TMB-high tumors showed prolonged progression-free survival in univariate [HR, 0.32; 95% confidence interval (CI), 0.12-0.90] and multivariate (HR, 0.21; 95% CI, 0.07-0.69) analyses. In area under the receiver operating curve (AUC) analysis of TMB, PD-L1, EBV, MSI, and their combination, the AUC value was the highest for EBV (0.97), followed by MSI (0.96), PD-L1 (0.81), the combination (0.78), and TMB (0.56). Conclusion: In addition to EBV, MSI, and PD-L1 CPS, TMB could be used as a predictive biomarker in patients with advanced gastric cancer treated with ICB and may aid clinical decision making.

Project description:Background:Treatment with immune checkpoint blockade (ICB) with agents such as anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), and/or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) can result in impressive response rates and durable disease remission but only in a subset of patients with cancer. Expression of PD-L1 has demonstrated utility in selecting patients for response to ICB and has proven to be an important biomarker for patient selection. Tumor mutation burden (TMB) is emerging as a potential biomarker. However, refinement of interpretation and contextualization is required. Materials and methods:In this review, we outline the evolution of TMB as a biomarker in oncology, delineate how TMB can be applied in the clinic, discuss current limitations as a diagnostic test, and highlight mechanistic insights unveiled by the study of TMB. We review available data to date studying TMB as a biomarker for response to ICB by tumor type, focusing on studies proposing a threshold for TMB as a predictive biomarker for ICB activity. Results:High TMB consistently selects for benefit with ICB therapy. In lung, bladder and head and neck cancers, the current predictive TMB thresholds proposed approximate 200 non-synonymous somatic mutations by whole exome sequencing (WES). PD-L1 expression influences response to ICB in high TMB tumors with single agent PD-(L)1 antibodies; however, response may not be dependent on PD-L1 expression in the setting of anti-CTLA4 or anti-PD-1/CTLA-4 combination therapy. Disease-specific TMB thresholds for effective prediction of response in various other malignancies are not well established. Conclusions:TMB, in concert with PD-L1 expression, has been demonstrated to be a useful biomarker for ICB selection across some cancer types; however, further prospective validation studies are required. TMB determination by selected targeted panels has been correlated with WES. Calibration and harmonization will be required for optimal utility and alignment across all platforms currently used internationally. Key challenges will need to be addressed before broader use in different tumor types.

Dataset Information

High tumor mutation burden predicts better efficacy of immunotherapy: a pooled analysis of 103078 cancer patients.

Publications

High tumor mutation burden predicts better efficacy of immunotherapy: a pooled analysis of 103078 cancer patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets