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The trial that made immunotherapy alone, with no chemotherapy, the first treatment for the 5% of bowel cancers with a broken DNA spell-checker. Over half of patients were alive at five years.
Pembrolizumab doubled median PFS (16.5 vs 8.2 months, HR 0.60) and at 5-year follow-up (Annals of Oncology 2024) median OS was 77.5 months with a 5-year OS of 54.8%, despite 62% of chemotherapy patients crossing over to anti-PD-1 therapy. First-line FDA approval June 2020. ESMO-MCBS grade 4. The comparator arm's crossover means the OS hazard ratio (0.73) understates the benefit.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
307 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Progression-free survivalprimary | Pembrolizumab | 153 | 16.5 months | 0.6 (0.45 to 0.8) | - | link |
| Chemotherapy | 154 | 8.2 months | ||||
| Overall survival (5-year follow-up) | Pembrolizumab | 153 | 77.5 months | 0.73 | - | link |
| Chemotherapy | 154 | 36.7 months |
This is the European standard the UK and NHS page for colorectal cancer is compared against; NICE NG151 covers the same ground for England with a narrower set of funded drugs.
A second publication from the KEYNOTE-177 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.
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 metastatic colorectal cancers that are mismatch-repair proficient (the deficient share is higher in localised disease, about 15%).
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.
It fixes the metastatic prevalence figures every subsequent trial design has used, and it separates two biomarkers that travel together: BRAF, not mismatch repair deficiency, is what makes the prognosis bad.
Shares CheckMate 142, Thierry André, Making microsatellite-stable colorectal cancer immunotherapy-responsive, Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval.
Shares Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval, KEYNOTE-177: pembrolizumab instead of chemotherapy as first treatment for mismatch-repair-deficient metastatic colorectal cancer, Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ, Mismatch repair deficient (MSI-high) pancreatic ductal adenocarcinoma.
Shares Making microsatellite-stable colorectal cancer immunotherapy-responsive, Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ, Cold tumours and the immunosuppressive microenvironment, No one can predict who responds to immunotherapy.
Shares Le 2017: mismatch-repair deficiency predicts response to PD-1 blockade across twelve tumour types, leading to the first tissue-agnostic drug approval, KEYNOTE-177: pembrolizumab instead of chemotherapy as first treatment for mismatch-repair-deficient metastatic colorectal cancer, Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ, Mismatch-repair deficient (MSI-high) colorectal cancer.
Shares Making microsatellite-stable colorectal cancer immunotherapy-responsive, Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ, Cold tumours and the immunosuppressive microenvironment, No one can predict who responds to immunotherapy.
Shares Thierry André, KEYNOTE-177: pembrolizumab instead of chemotherapy as first treatment for mismatch-repair-deficient metastatic colorectal cancer, Mismatch-repair deficient (MSI-high) colorectal cancer, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR).
Shares Le 2015: PD-1 blockade works in tumours with mismatch-repair deficiency, whatever the organ, No one can predict who responds to immunotherapy, Mismatch-repair deficient (MSI-high) colorectal cancer, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR).
Shares Making microsatellite-stable colorectal cancer immunotherapy-responsive, Cold tumours and the immunosuppressive microenvironment, No one can predict who responds to immunotherapy, Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR).