Dung T. Le
First author of the studies that showed mismatch-repair-deficient tumours respond to PD-1 blockade regardless of origin.
Led the KEYNOTE-016 study and its extension establishing pembrolizumab's tissue-agnostic activity in dMMR tumours; also works on GVAX and pancreatic cancer vaccines.
| Title | Journal | Year |
|---|---|---|
| PD-1 blockade in tumors with mismatch-repair deficiency | New England Journal of Medicine | 2015 |
Every colorectal cancer should be tested for mismatch repair deficiency, because patients whose metastatic tumour is dMMR should receive pembrolizumab rather than chemotherapy as first treatment, gaining a much better chance of durable remission with fewer side effects. About a third of dMMR tumours do not respond initially, so early scans are essential and chemotherapy remains available. The trial does not apply to the 95% of colorectal cancers that are mismatch-repair proficient.
This paper established a new regulatory paradigm: a drug approved for a molecular feature regardless of organ. It made MSI/MMR testing standard across advanced cancers and remains the clearest example of a biomarker that works across histologies. It also anchored the idea that mutation load, via neoantigens, is what makes tumours visible to T cells.
This small trial explained why colorectal cancer had seemed immune-resistant (most is MMR-proficient) and established the principle that a genomic feature, not the tissue of origin, can predict immunotherapy response. It led directly to the 2017 tissue-agnostic approval of pembrolizumab and to routine MMR/MSI testing of many cancers. Every patient with advanced dMMR cancer should now be considered for checkpoint blockade.
Pages like this
not linked directly; found by shared links- PersonLuis A. Diaz Jr.
Shares Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ, KEYNOTE-177: pembrolizumab instead of chemotherapy as first treatment for mismatch-repair-deficient metastatic colorectal cancer, Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval, PD-1.
- TrialKEYNOTE-177
Shares Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval, PD-1, Pembrolizumab, Colorectal cancer.
- PersonDrew M. Pardoll
Shares Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ, Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center, PD-1.
- PersonJulie R. Brahmer
Shares Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center, PD-1, Pembrolizumab.
- TrialCheckMate 8HW
Shares Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval, PD-1, Colorectal cancer.
- PersonElizabeth M. Jaffee
Shares Johns Hopkins Hospital / Sidney Kimmel Comprehensive Cancer Center, Pancreatic ductal adenocarcinoma.
- ProductOlomorasib
Shares Pembrolizumab, Pancreatic ductal adenocarcinoma, Colorectal cancer.
- Key paperCercek 2022: six months of dostarlimab alone made rectal cancer disappear in every patient with mismatch-repair deficiency
Shares Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ, PD-1, Pembrolizumab, Colorectal cancer.