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The follow-up that took the same test across 12 different cancers and found the same answer, producing the first drug approval in history based on a molecular feature rather than an organ.
Le, Durham, Smith and colleagues expanded the 2015 proof-of-concept study to evaluate PD-1 blockade in patients with advanced mismatch repair-deficient cancers across 12 different tumour types. Functional analysis in a responding patient demonstrated rapid in vivo expansion of neoantigen-specific T cell clones reactive to mutant neopeptides found in the tumour.
The authors concluded that the large proportion of mutant neoantigens in mismatch repair-deficient cancers makes them sensitive to immune checkpoint blockade regardless of tissue of origin, the argument the United States Food and Drug Administration accepted in granting pembrolizumab its tissue-agnostic approval in May 2017.
The first tumour-agnostic approval, and the reason every patient with metastatic colorectal cancer has mismatch repair status tested regardless of where the tumour started.
Shares Luis A. Diaz Jr., PD-1 blockade in tumors with mismatch-repair deficiency, Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR) and the tag colorectal-evidence.
Shares PD-1 blockade in tumors with mismatch-repair deficiency, Neoantigen, No one can predict who responds to immunotherapy, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR) and the tag colorectal-evidence.
Shares PD-1 blockade in tumors with mismatch-repair deficiency, No one can predict who responds to immunotherapy, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation and the tag colorectal-evidence.
Shares Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Mismatch-repair deficient (MSI-high) colorectal cancer, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation and the tag colorectal-evidence.
Shares Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Mismatch-repair deficient (MSI-high) colorectal cancer, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation and the tag colorectal-evidence.
Shares Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2), Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Mismatch-repair deficient (MSI-high) colorectal cancer, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation and the tag colorectal-evidence.
Shares Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR), Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation, Colorectal cancer and the tag colorectal-evidence.
Shares Rare and paediatric cancers without markets, Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation, Colorectal cancer and the tag colorectal-evidence.