Who is this trial for?
This trial was for adults with the most common kind of advanced lung cancer, who had not yet had treatment for it and did not have certain gene changes.
People in the trial had:
- Non-squamous non-small-cell lung cancer (NSCLC) that had spread (metastatic).
- No EGFR or ALK gene changes — these have their own targeted pill treatments, so this trial was for people without them.
- No previous treatment for the advanced cancer, and were well enough for daily life.
What kind of trial is this?
This trial tested a new combination for treating cancer that had already spread.
Background: why researchers asked this question
For advanced lung cancer without targetable gene changes, the standard first treatment was chemotherapy. A type of immunotherapy called a PD-1 inhibitor (pembrolizumab) helped too, but on its own it worked best only for tumours with high levels of a protein called PD-L1 — a minority of patients.
Researchers wondered whether combining immunotherapy with chemotherapy from the start could help a broader group of people — including those with low PD-L1 levels.
The trial: what was tested and how
KEYNOTE-189 enrolled 616 people across 16 countries. They were assigned at random (2 to 1) to one of two groups:
- Immunotherapy + chemo: pembrolizumab added to standard chemotherapy.
- Chemo + placebo: the same chemotherapy plus a dummy infusion.
Neither patients nor doctors knew who was getting immunotherapy (this is called “double-blind,” which makes the comparison especially fair). People in the chemo group whose cancer grew could later “cross over” to receive immunotherapy. The main measures were how long people lived and how long before the cancer grew.
An oncologist's perspective
Velma was a 60 yo woman who had been smoking since she was 14. She had a chronic cough, but it was getting worse, and sometimes now there would be spots of blood. More concerning was her weight loss - in the past few weeks food was unappetizing, and her clothes hung too loosely. A simple x-ray prompted a whole slew of investigations, including a biopsy. Lung cancer was ravaging her, and when I met her in the clinic, it was with faint hope that there was anything that could be done to help her.
Results: what they found
Adding immunotherapy helped people live longer and kept the cancer controlled longer — and the benefit held across PD-L1 levels.
Immunotherapy + chemo vs chemo alone
Far more people were alive at one year with immunotherapy added — about a 50% lower risk of dying during the study.
The cancer stayed controlled almost twice as long with immunotherapy added.
More than twice as many people had their tumours shrink with the combination.
The benefit was seen across all PD-L1 levels, including tumours with low PD-L1 — a group that often gets little from immunotherapy alone. Serious side effects were similar overall between the groups, though immunotherapy added some immune-related effects and a small increase in kidney problems.
One thing to keep in mind about timing
These were the results from an early (first interim) look at the trial in 2018, after about 10 months of follow-up. This combination went on to become a widely used first-line standard for this type of lung cancer.
The bottom line
For people with advanced non-squamous lung cancer without EGFR or ALK changes, adding immunotherapy (pembrolizumab) to standard chemotherapy helped people live longer, kept the cancer controlled longer, and shrank more tumours — across all PD-L1 levels. This was a practice-changing result.
What this could mean for you
- Gene testing comes first. This approach is for people without EGFR or ALK changes — those are usually tested for, because they have their own targeted treatments.
- It doesn't help everyone. Immunotherapy has its own side effects, including the immune system occasionally attacking healthy organs.
- It's now a standard option. Combining immunotherapy with chemotherapy is widely used as a first treatment for this type of lung cancer.
An oncologist's perspective
Lung cancer used to be a death sentence. Patients like Velma did not do well with standard chemotherapy, and we would watch helplessly as the disease took its toll over the course of a few months. Now, with the addition of drugs like pembrolizumab, and new oral regimens as well, patients like Velma have a much better chance. Yes, the chemo is tough, and pembrolizumab can add some more side effects — but the chance of living beyond five years is no longer impossible, with a meaningful benefit to quality of life.
Questions & comments
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