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Plasma Versus Tissue Tumor Mutational Burden As Biomarkers Of Durvalumab Plus Tremelimumab Response In Patients With Metastatic Colorectal Cancer In The Co.26 Trial.

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Plasma Versus Tissue Tumor Mutational Burden As Biomarkers Of Durvalumab Plus Tremelimumab Response In Patients With Metastatic Colorectal Cancer In The Co.26 Trial.

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Plasma versus Tissue Tumor Mutational Burden as Biomarkers of Durvalumab plus Tremelimumab Response in Patients with

Jonathan M Loree¹, Emma Titmuss¹, James T Topham¹

¹BC Cancer, University of British Columbia, Vancouver, Canada.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research

|May 10, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

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Plasma tumor mutation burden (pTMB) may predict immunotherapy benefit in colorectal cancer (CRC), unlike tissue TMB. This study found specific pTMB thresholds associated with improved outcomes in CRC patients treated with durvalumab and tremelimumab.

Area of Science:

Oncology
Genomics
Immunotherapy

Background:

Tissue-derived tumor mutation burden (TMB) ≥10 mutations/Mb is an established biomarker for immune checkpoint inhibitor (ICI) therapy.
Its utility in colorectal cancer (CRC) and the role of plasma TMB (pTMB) remain less defined.

Purpose of the Study:

To evaluate the predictive value of tissue and plasma TMB for immunotherapy response in microsatellite stable (MSS) metastatic CRC.
To identify optimal TMB thresholds for stratifying patients in the CO.26 trial.

Main Methods:

A randomized phase II study (CO.26) compared durvalumab and tremelimumab (D + T) with best supportive care (BSC).
Tissue and plasma TMB (pTMB) were assessed using next-generation sequencing.
Optimal thresholds were determined using a minimal P value approach for overall survival (OS) analysis.

Main Results:

Tissue TMB ≥10 mutations/Mb did not predict benefit from D + T in MSS metastatic CRC (HR, 0.71; P = 0.47).
Plasma TMB (pTMB) ≥28 mutations/Mb was predictive of benefit (HR, 0.34; P = 0.022).
Clonal pTMB ≥10.6 mutations/Mb and subclonal pTMB ≥25.9 mutations/Mb also predicted benefit (P = 0.029 and P = 0.010, respectively).

Conclusions:

Plasma TMB (pTMB), derived from either clonal or subclonal mutations, shows potential as a predictive biomarker for immunotherapy in CRC.
Tissue TMB lacked predictive utility in this study population.
Further validation is required to confirm pTMB's role in guiding ICI treatment decisions for CRC.