The role of immune checkpoint inhibitors for patients with advanced stage microsatellite stable colorectal cancer and high tumor mutation burden: quantity or quality?

Autor:	Vegivinti CTR; Department of Medicine, Jacobi Medical Center/Albert Einstein College of Medicine, New York, New York, USA., Gonzales Gomez C; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Syed M; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Ferrell M; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Cheng S; Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Singhi A; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Saeed A; Division of Hematology/Oncology, Department of Medicine University of Pittsburgh School of Medicine Pittsburgh, Pittsburgh, PA, USA., Sahin IH; Division of Hematology/Oncology, Department of Medicine University of Pittsburgh School of Medicine Pittsburgh, Pittsburgh, PA, USA.
Jazyk:	angličtina
Zdroj:	Expert opinion on biological therapy [Expert Opin Biol Ther] 2023 Jul-Dec; Vol. 23 (7), pp. 595-601. Date of Electronic Publication: 2023 Jun 18.
DOI:	10.1080/14712598.2023.2226327
Abstrakt:	Introduction: The US Food and Drug Administration (FDA) approved pembrolizumab for patients with unresectable or metastatic solid tumors with tumor mutational burden (TMB) of ≥ 10 mutations/megabase. However, the clinical implications of this universal cutoff of TMB ≥ 10 for patients with microsatellite stable (MSS) metastatic colorectal cancer (CRC) remain debatable. Areas Covered: In this review, we discuss the tissue agnostic approval of pembrolizumab, its efficacy, and clinical relevance in the management of patients with MSS CRC patients with high TMB (defined as TMB ≥ 10). We also elaborate on molecular subgroups of MSS CRC that influence the immune checkpoint inhibitor (ICI) response for patients with MSS CRC, including pathogenic POLE and POLD1 mutations associated with ultramutated tumors. Expert Opinion: Patients with microsatellite stable CRC with TMB ≥ 10 without POLE and POLD1 mutations may not significantly benefit from immune checkpoint inhibitors therapy. Predetermined cutoff TMB ≥ 10 mutation per MB does not seem to define a universal cutoff for the benefit of disease-agnostic ICI therapy, particularly for patients with MSS CRC. Patients with POLE/POLD1 mutations with MSS CRC represent a unique biological subgroup of MSS CRC with favorable responses to ICI therapy.
Databáze:	MEDLINE
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