This study compared immunotherapy with pembrolizumab against chemotherapy in people with advanced bowel (colorectal) cancer whose tumour had a particular feature in how it repairs DNA (MSI-H or dMMR) and who had not yet been treated. In the pembrolizumab group the disease stayed under control for longer, and fewer serious side effects occurred (severe side effects 22% versus 66%). For overall length of life, the difference between the two groups was not statistically clear; however, about 60% of patients in the chemotherapy group later switched to immunotherapy. Be sure to talk to your own doctor about whether this treatment is right for you.
MSI-H/dMMR metastatic colorectal cancer; first-line (in ESMO 2026, when dual therapy is not possible)
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Pembrolizumab | 200 mg every 3 weeks or 400 mg every 6 weeks | IV | Day 1 |
Dose from the FDA label for pembrolizumab; in KEYNOTE-177, 200 mg every 3 weeks for up to 35 doses.
On the page “Colorectal cancer” · MSI-H/dMMR metastatic colorectal cancer: first-line
First-line; cetuximab or panitumumab only for RAS wild-type disease (especially left-sided tumours); bevacizumab for RAS-mutant or right-sided tumours
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Oxaliplatin | 85 mg/m² | IV over 2 h | Day 1 |
| Leucovorin | 400 mg/m² | IV over 2 h | Day 1 |
| Fluorouracil (bolus) | 400 mg/m² | IV bolus | Day 1 |
| Fluorouracil (infusion) | 2400 mg/m² | IV, continuous 46-h infusion | Starting day 1 |
| Plus one of these drugs | |||
| Bevacizumab | 5 mg/kg | IV | Day 1 |
| Cetuximab | 500 mg/m² over 120 min (or 400 mg/m², then 250 mg/m² weekly) | IV | Day 1 |
| Panitumumab | 6 mg/kg over 60 min (doses above 1000 mg: 90 min) | IV | Day 1 |
Doses of mFOLFOX6 with bevacizumab 5 mg/kg or with cetuximab from KEYNOTE-177; per the European SmPC, the bevacizumab dose in metastatic colorectal cancer is 5 or 10 mg/kg every 2 weeks or 7.5 or 15 mg/kg every 3 weeks; cetuximab; panitumumab with FOLFOX in the first line for RAS wild-type disease.
On the page “Colorectal cancer” · pMMR/MSS metastatic colorectal cancer: first-line
First- or second-line metastatic disease; cetuximab only for RAS wild-type disease
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Irinotecan | 180 mg/m² | IV over 90 min | Day 1 |
| Leucovorin | 400 mg/m² | IV | Day 1 |
| Fluorouracil (bolus) | 400 mg/m² | IV bolus | Day 1 |
| Fluorouracil (infusion) | 1200 mg/m² per day for 2 days (2400 mg/m²) | IV, continuous infusion | Days 1 and 2 |
| Plus one of these drugs | |||
| Bevacizumab | 5 mg/kg | IV | Day 1 |
| Cetuximab | 500 mg/m² every 2 weeks, or 400 then 250 mg/m² weekly | IV | Day 1 |
Doses of FOLFIRI and bevacizumab from KEYNOTE-177; cetuximab with FOLFIRI per the FDA label; after progression on a bevacizumab-containing regimen, bevacizumab 5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks can be continued with irinotecan- or oxaliplatin-based backbone chemotherapy.
On the page “Colorectal cancer” · pMMR/MSS metastatic colorectal cancer: first-line
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Pembrolizumab 200 mg IV on day 1 of each 21-day cycle (every 3 weeks), until disease progression, unacceptable toxicity or a maximum of 35 cycles (about 2 years); 153 patients. Patients who progressed after stopping treatment with stable disease could receive a second course of pembrolizumab for up to 17 more cycles.
154 patients; one of the two regimens below every 2 weeks, with or without bevacizumab or cetuximab at the investigator's choice:
• mFOLFOX6 IV: oxaliplatin 85 mg/m² day 1, leucovorin 400 mg/m² day 1, and fluorouracil 400 mg/m² bolus day 1, then continuous infusion 1200 mg/m² per day for 2 days (days 1 and 2).
• FOLFIRI IV: irinotecan 180 mg/m² day 1, leucovorin 400 mg/m² day 1, and fluorouracil 400 mg/m² bolus day 1, then continuous infusion 1200 mg/m² per day for 2 days (days 1 and 2).
• Optional addition of bevacizumab IV 5 mg/kg every 2 weeks, or cetuximab IV weekly (first dose 400 mg/m², then 250 mg/m² for each subsequent dose).
Chemotherapy-group patients could cross over to pembrolizumab for up to 35 cycles after disease progression.
Source of the regimen details: Abstract and full text of the paper (PMC9533375) and ClinicalTrials.gov NCT02563002 (number of pembrolizumab cycles and cetuximab infusion duration)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Patients aged 18 years or older with ECOG performance status 0 or 1 and previously untreated microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) metastatic colorectal cancer. Of 852 patients screened, 307 (36%) were randomised (11 February 2016 to 19 February 2018).
Dual primary endpoints: overall survival (OS) and progression-free survival (PFS) in the intention-to-treat (ITT) population. The aim of this analysis was to report the final overall survival analysis.
Treatment-related grade 3 or higher adverse events occurred in 33 (22%) of 153 patients in the pembrolizumab group versus 95 (66%) of 143 patients in the chemotherapy group.
Most common grade 3 or higher events attributed to pembrolizumab: increased alanine aminotransferase, colitis, diarrhoea and fatigue, each in 3 patients (2%). In the chemotherapy group: decreased neutrophil count (24 patients; 17%), neutropenia (22 patients; 15%), diarrhoea (14 patients; 10%) and fatigue (13 patients; 9%).
Serious adverse events attributed to study treatment occurred in 25 patients (16%) in the pembrolizumab group and 41 patients (29%) in the chemotherapy group. There were no deaths attributed to pembrolizumab; one death from intestinal perforation was attributed to chemotherapy.
This final analysis showed that pembrolizumab has durable antitumour activity and fewer grade 3 or higher adverse events than chemotherapy, and the authors regard it as an effective first-line treatment for MSI-H or dMMR metastatic colorectal cancer. However, statistical superiority in overall survival was not demonstrated (HR 0.74; p=0.036 with a prespecified α of 0.025), and the extensive crossover (60%) must be taken into account in interpretation. Regulatory approval status and clinical guideline recommendations should be checked separately in up-to-date sources; the abstract does not address them.
The study was open-label. 60% of chemotherapy-group patients crossed over to anti-PD-1 or anti-PD-L1 therapy (37 to treatment outside the study), which may affect the overall survival comparison. The overall survival difference was not statistically significant (the prespecified α of 0.025 was not met). Chemotherapy was investigator's choice, with or without targeted agents.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.
Who are you reading this site as?
Your choice applies to every page; change it any time from the bottom of the page.
Type to search...