Emerging treatments
Targeted therapy and immunotherapy for biomarker-specified subgroups
A patient with test results (mismatch repair deficiency [dMMR] or microsatellite instability-high [MSI-H], tumor mutational burden-high [TMB-H]) predictive for efficacy of immune checkpoint inhibitors or targeted therapies may be a candidate for therapy with the following agents: pembrolizumab, a programmed death receptor-1 (PD-1)-blocking monoclonal antibody approved for unresectable or metastatic dMMR or MSI-H solid tumors, and unresectable or metastatic TMB-H solid tumors (defined as at least 10 mutations per megabase); dostarlimab, a PD-1-blocking monoclonal antibody approved for the treatment of dMMR solid tumors; entrectinib and larotrectinib, small molecule tropomyosin receptor kinase (TRK) inhibitors approved for the treatment of unresectable or metastatic neurotrophic receptor tyrosine kinase (NRTK)-positive solid tumors; the combination of dabrafenib (a BRAF kinase inhibitor) plus trametinib (a mitogen-activated protein kinase [MEK] inhibitor) approved for the treatment of unresectable or metastatic BRAF V600E-mutation-positive solid tumors; selpercatinib (a Ret proto-oncogene [RET] inhibitor), approved for the treatment of locally advanced or metastatic RET fusion-positive solid tumors; fam-trastuzumab deruxtecan (a monoclonal antibody-drug conjugate targeting HER2), approved for the treatment of unresectable or metastatic HER2-positive (IHC 3+) solid tumors.[15][57] These treatments are generally approved for patients who have progressed on prior treatment, or for whom no other treatments are available.
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