Mismatch-repair deficient (MSI-high) colorectal cancer: the decisions you may face
4 treatment settings, 3 with more than one named option. Each section lays out the options the standard of care names, what each is for, the trials behind them with their recorded results, the side effects and cautions on record, and questions to ask. Built from the cancer page's standard-of-care rows; nothing here is advice for your case.
Metastatic, first line
Pembrolizumab alone (KEYNOTE-177) or nivolumab plus ipilimumab (CheckMate 8HW); chemotherapy only if immunotherapy is contraindicated.
Pembrolizumab is a PD-1 blocking antibody approved in more than 40 settings, from melanoma and lung cancer to the first tumour-agnostic approval for mismatch-repair-deficient tumours in 2017, and before and after surgery in triple-negative breast cancer. A subcutaneous form arrived in 2025, and it is the backbone partner for ADCs and personalised neoantigen vaccines.
Nivolumab was the second PD-1 blocker and is often combined with ipilimumab. Long-term data show about half of advanced melanoma patients alive at 10 years on the combination.
Ipilimumab was the first checkpoint inhibitor (2011), and proved the immune system could be unleashed against cancer.
Immune checkpoint inhibitors are antibodies against CTLA-4, PD-1 or PD-L1 that release the brakes on T cells so they attack the cancer. They are approved in more than 20 tumour types and produce lasting, sometimes curative responses that chemotherapy rarely does, but most patients do not respond and autoimmune side effects are the cost.
- Durable, sometimes curative responses
- Broad applicability
- First-line MSI-H/dMMR metastatic colorectal cancer: pembrolizumab vs investigator-choice chemotherapy
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- PFS 16.5 vs 8.2 months (HR 0.60); 5-year OS 54.8%, median OS 77.5 months.
Progression-free survival (months): Pembrolizumab 16.5 (n=153) vs Chemotherapy 8.2 (n=154) · HR 0.6 · source - Tests Nivolumab, IpilimumabMSI-H/dMMR metastatic colorectal cancer, all lines: nivolumab + ipilimumab vs nivolumab vs chemotherapy
First-line PFS 54.1 vs 5.9 months (HR 0.21); combination vs nivolumab PFS HR 0.62.
Progression-free survival, first line (months): Nivolumab + ipilimumab 54.1 (n=202) vs Chemotherapy 5.9 (n=101) · HR 0.21 · source
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Hypothyroidism (immune-mediated) · Pooled monotherapy data, >2,800 patients | 8% | - |
| Pneumonitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 3.4% | - |
| Colitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 1.7% | - |
| Hepatitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 0.7% | - |
- No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Colitis with ipilimumab (1+3 mg/kg) · Monotherapy pooled unless stated | 25% | 14.4% |
| Hepatitis with ipilimumab · Monotherapy pooled unless stated | 15% | 13.4% |
| Colitis · Monotherapy pooled unless stated | 2.9% | 1.7% |
| Hepatitis · Monotherapy pooled unless stated | 1.8% | 1.5% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Colitis (with nivolumab 1+3) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 25% | 14.4% |
| Hepatitis (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 15% | 13.4% |
| Rash (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 28% | 4.8% |
| Adrenal insufficiency (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 8% | 2.6% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Most patients do not respond
- Autoimmune toxicity
- Biomarkers are imperfect
- Between Pembrolizumab, Nivolumab, Ipilimumab and the other options, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in KEYNOTE-177 and CheckMate 8HW, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- Which side effects of Pembrolizumab or Nivolumab are most likely for me, which are reversible, and which would make us stop?Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Colon Cancer), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (metastatic, first line), which of the standard options do you recommend and why?Why: Guideline options include: Pembrolizumab alone (KEYNOTE-177) or nivolumab plus ipilimumab (CheckMate 8HW); chemotherapy only if immunotherapy is contraindicated.
- Am I a candidate for Pembrolizumab, Nivolumab, Ipilimumab, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of KEYNOTE-177 and CheckMate 8HW apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.
Localised colon cancer
Neoadjuvant nivolumab plus ipilimumab for locally advanced tumours (NICHE-2) where available; surgery; adjuvant FOLFOX plus atezolizumab for stage III (ATOMIC); no fluoropyrimidine alone.
Nivolumab was the second PD-1 blocker and is often combined with ipilimumab. Long-term data show about half of advanced melanoma patients alive at 10 years on the combination.
Ipilimumab was the first checkpoint inhibitor (2011), and proved the immune system could be unleashed against cancer.
A PD-L1 blocker used in lung, liver, and bladder cancer. In 2026 it became the first drug approved based on a blood test showing leftover cancer after bladder surgery.
FOLFOX is the workhorse chemotherapy combination for bowel cancer, used after surgery to cure and in advanced disease as the backbone that targeted drugs are added to.
- Tests Nivolumab, IpilimumabLocally advanced (mostly stage III) dMMR colon cancer: 4 weeks of neoadjuvant nivolumab + one dose ipilimumab, then surgery
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- pCR 68%, major pathologic response 95%; 3-year DFS 100%.
- Resected stage III dMMR colon cancer: adjuvant FOLFOX + atezolizumab (12 months) vs FOLFOX
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- 3-year DFS 86.4% vs 76.6%, HR 0.50.
Disease-free survival at 3 years (percent): FOLFOX + atezolizumab 86.4 (n=355) vs FOLFOX 76.6 (n=357) · HR 0.5 · source
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Colitis with ipilimumab (1+3 mg/kg) · Monotherapy pooled unless stated | 25% | 14.4% |
| Hepatitis with ipilimumab · Monotherapy pooled unless stated | 15% | 13.4% |
| Colitis · Monotherapy pooled unless stated | 2.9% | 1.7% |
| Hepatitis · Monotherapy pooled unless stated | 1.8% | 1.5% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Colitis (with nivolumab 1+3) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 25% | 14.4% |
| Hepatitis (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 15% | 13.4% |
| Rash (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 28% | 4.8% |
| Adrenal insufficiency (with nivolumab) · Nivolumab 1 mg/kg + ipilimumab 3 mg/kg, melanoma | 8% | 2.6% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Pneumonitis (immune-mediated) · Monotherapy pooled | 3% | 0.8% |
| Hepatitis (immune-mediated) · Monotherapy pooled | 1.8% | 0.7% |
| Colitis (immune-mediated) · Monotherapy pooled | 1% | 0.5% |
| Hypothyroidism (immune-mediated) · Monotherapy pooled | 4.9% | 0.2% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Between Nivolumab, Ipilimumab, Atezolizumab and the other options, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in NICHE-2 and ATOMIC (Alliance A021502), and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- Which side effects of Nivolumab or Ipilimumab are most likely for me, which are reversible, and which would make us stop?Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Colon Cancer), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (localised colon cancer), which of the standard options do you recommend and why?Why: Guideline options include: Neoadjuvant nivolumab plus ipilimumab for locally advanced tumours (NICHE-2) where available; surgery; adjuvant FOLFOX plus atezolizumab for stage III (ATOMIC); no fluoropyrimidine alone.
- Am I a candidate for Nivolumab, Ipilimumab, Atezolizumab or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of NICHE-2 and ATOMIC (Alliance A021502) apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.
Rectal cancer
Six months of dostarlimab or another PD-1 antibody with non-operative management for complete responders (AZUR-1).
Dostarlimab is a PD-1 blocker famous for making rectal cancer disappear without surgery in every patient with a mismatch-repair-deficient tumour.
- Tests DostarlimabUntreated stage II/III dMMR/MSI-H locally advanced rectal cancer: dostarlimab monotherapy for 6 months, no surgery or radiation if complete response
Primary endpoint (sustained cCR at 12 months) met; rates pending congress presentation.
No side-effect rates or interaction flags are recorded for these options yet. The side-effect lookup and interaction checker cover the products that have them.
- Is Dostarlimab the only reasonable path for me, or is there a trial, a different sequence or a wait-and-see option?Why: A single standard does not mean a single choice; timing and trials are decisions too.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in AZUR-1, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Rectal Cancer), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (rectal cancer), which of the standard options do you recommend and why?Why: Guideline options include: Six months of dostarlimab or another PD-1 antibody with non-operative management for complete responders (AZUR-1).
- Am I a candidate for Dostarlimab, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of AZUR-1 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.
Lynch syndrome carriers
Colonoscopy every one to two years from age 25 (earlier for MLH1 and MSH2), daily aspirin (CAPP2), cascade germline testing of relatives, hysterectomy and oophorectomy after childbearing for women.
Aspirin is not a cancer drug but sits in cancer care in two places: low doses prevent clots in polycythaemia vera and essential thrombocythaemia, and long-term use lowers colorectal cancer in people with Lynch syndrome, while a trial in the healthy elderly found no benefit and possible harm.
Finding and removing polyps before they become cancer. Colonoscopy prevents cancer; stool and blood tests catch it early and get more people screened.
- Colonoscopy both detects and prevents by polypectomy
- Non-invasive options raise participation
A test of the DNA you were born with, to find inherited risk genes such as BRCA or Lynch syndrome.
- Actionable for patient and relatives
- Cheap
Drugs or surgery for people at high inherited risk, before any cancer appears.
- Large absolute risk reduction in carriers
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
- Blood and stool tests miss most precancerous polyps
- Colonoscopy capacity and access
- Early-onset cancers arise before screening age
- VUS burden
- Uptake and counselling capacity
- Side effects deter uptake; surgery is irreversible
- Between Aspirin, Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood), Germline (hereditary) testing and the other options, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Colon Cancer), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (lynch syndrome carriers), which of the standard options do you recommend and why?Why: Guideline options include: Colonoscopy every one to two years from age 25 (earlier for MLH1 and MSH2), daily aspirin (CAPP2), cascade germline testing of relatives, hysterectomy and oophorectomy after childbearing for women.
- Am I a candidate for Aspirin, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Add these to your appointment list, or take the full question set for this cancer.