Who is this trial for?
This trial was for adults whose colon or rectal cancer had spread to other parts of the body, and whose tumour had a specific genetic feature.
People in the trial had all of the following:
- Colorectal cancer that had spread (also called metastatic, or stage IV) — meaning the cancer had moved beyond where it started.
- A tumour feature called MSI-H or dMMR (explained just below). Their tumour had been tested and found to have it.
- No treatment yet for the advanced cancer. The trial looked at the very first treatment a person receives — doctors call this "first-line."
- Well enough for daily life — generally up and about, able to care for themselves.
What kind of trial is this?
We sort trials into seven plain-language types. This one is about treating an existing cancer — testing whether a new treatment works better than the current standard.
Background: why researchers asked this question
For many years, the first treatment for advanced colorectal cancer was chemotherapy, sometimes combined with other targeted drugs. Chemo can shrink tumours and help people live longer, but it often stops working within a year or so, and it can be hard on the body.
Doctors noticed that tumours with the MSI-H/dMMR feature behave differently. Because these cancers carry so many DNA mistakes, the immune system can often spot them as "wrong" — if it gets a little help. That help can come from a kind of immunotherapy called a PD-1 inhibitor.
So researchers asked a clear question: for people with this specific type of advanced colorectal cancer, would starting with immunotherapy help them live longer than starting with chemotherapy?
The trial: what was tested and how
KEYNOTE-177 enrolled 307 adults with untreated MSI-H/dMMR metastatic colorectal cancer, at 193 hospitals across 23 countries. Each person was placed — at random, like a coin flip — into one of two groups:
- Immunotherapy group: pembrolizumab, given by IV every 3 weeks.
- Chemotherapy group: standard chemo, sometimes with an added targeted drug — whatever the patient's doctor judged best.
A few details matter for understanding the results:
- People could switch. If the cancer grew while on chemo, those patients were allowed to "cross over" and receive immunotherapy. In the end, about 62% of the chemo group went on to receive immunotherapy later. This makes the comparison harder for immunotherapy to win — so any survival gap that remains is especially meaningful.
- Everyone knew which treatment they were getting (this is called "open-label" — there was no dummy treatment).
- Long follow-up. This report followed people for more than 6 years on average, so we can see not just whether tumours shrank, but how long people actually lived.
The two main things researchers measured were how long people lived (overall survival) and how long before the cancer started growing again (progression-free survival). The first results were published in 2020; the long-term, five-year results are summarised here.
A note before the results
Testing for MSI-H/dMMR is now standard practice — it is done routinely on all colorectal cancer tissue. Even so, it is worth confirming with your team that it was done and asking what the result was. Most people will hear that their tumour does not have this feature, and for them the standard treatment path applies. But for the small group whose cancer is MSI-H, that result opens a very different door.
It is also worth knowing that MSI-H colorectal cancer can arise in two different ways. In some people it is inherited — this is called Lynch syndrome, a hereditary condition that significantly raises the lifetime risk of several cancers. In others, the same tumour feature develops on its own, with no inherited cause. Your oncologist can arrange further testing to find out which applies to you, and if Lynch syndrome is confirmed, it has important implications for your close relatives as well.
Results: what they found
After more than five years of follow-up, the immunotherapy group did clearly better on the measures that matter most.
Immunotherapy vs chemotherapy — key numbers
The typical person on immunotherapy lived more than twice as long — about 6½ years versus about 3 years. 54.8% of the immunotherapy group were still alive at 5 years, compared with 44.2% on chemo.
The cancer stayed controlled about twice as long with immunotherapy. Roughly 1 in 3 people on immunotherapy still had no cancer growth at 5 years.
When immunotherapy worked, it tended to keep working for years. Most people who responded to it were still benefiting more than two years later.
Serious (grade 3–5) treatment-related side effects were about three times less common with immunotherapy. There were no treatment-related deaths in the immunotherapy group.
What do "the odds were lower" numbers (hazard ratios) mean?
Researchers also report a "hazard ratio." For living longer, it was 0.73 — roughly a 27% lower risk of dying at any point in time with immunotherapy. For the cancer growing, it was 0.60 — about a 40% lower risk of the cancer progressing. A number below 1 favours immunotherapy.
One honest caveat: not everything reached the strict bar for "statistically certain" in every analysis, partly because so many chemo patients later switched to immunotherapy. But the pattern was strong and consistent.
Not everyone benefited. Immunotherapy doesn't work for every person, and it has its own kind of side effects (the immune system can sometimes attack healthy organs, such as the thyroid or bowel). But for many people, the benefit was deep and lasting in a way that chemotherapy rarely achieves in this disease.
The bottom line
For the small group of people whose advanced colorectal cancer is MSI-H/dMMR, starting treatment with immunotherapy (pembrolizumab) instead of chemotherapy helped them live much longer, kept the cancer controlled longer, and caused fewer serious side effects. This is now a standard first-line option for this group.
What this could mean for you
- Testing is the key step. This approach only helps tumours with the MSI-H/dMMR feature. If you or a loved one has advanced colorectal cancer, it is reasonable to ask whether the tumour has been tested for MSI or mismatch repair.
- It's a specific group. Only about 1 in 20 advanced colorectal cancers carry this feature. For the other 19, chemotherapy and other treatments remain the better-studied path.
- Availability differs by place. Whether and how immunotherapy is funded varies by country and region. Your oncology team can explain the options where you live.
An oncologist's perspective
Although only about 5% of patients with metastatic colorectal cancer have MSI-H disease, that group is now treated in a completely different way — without traditional chemotherapy upfront. Seeing the benefits of pembrolizumab in these patients has been a game changer in the colon cancer field. Some day, hopefully, we will be able to expand the power of checkpoint inhibitor therapy to all colorectal cancer patients.
Questions & comments
Have a question about this trial? Ask below. Questions are read and answered by the site. We can't give personal medical advice, but we're glad to explain the research more clearly.