KEYNOTE-189: What the Lung Cancer Trial Found

A five-year figure that used to be unthinkable

Metastatic lung cancer was, for most of its history, measured in months. KEYNOTE-189 followed its patients for more than five years. At that point 19.4% of the group who had pembrolizumab added to chemotherapy were still alive, against 11.3% of those who had chemotherapy alone.

Roughly one in five. It is a small number until you place it next to what the same diagnosis meant twenty years ago.

Who was in the trial

616 people with previously untreated metastatic non-squamous non-small-cell lung cancer took part. All were tested first: anyone with an EGFR or ALK change in their tumor was excluded, because those cancers are treated with targeted drugs instead.

They were assigned 2 to 1. 410 received pembrolizumab and 206 received a placebo, both on top of pemetrexed with either carboplatin or cisplatin.

The five-year numbers

Median time from randomisation to the data cutoff in March 2022 was 64.6 months.

The hazard ratio for death was 0.60 (95% CI 0.50 to 0.72). For the cancer growing it was 0.50 (95% CI 0.42 to 0.60). Both favour adding pembrolizumab, and both are close to a one-third to one-half reduction in risk at any given moment.

57 people completed the full 35 cycles of pembrolizumab. Among them, 86.0% had their tumor shrink, and 71.9% were alive three years after finishing.

Where the median figures come from

The five-year report gives hazard ratios rather than medians. For those, you have to look at the earlier update, published after a median follow-up of 23.1 months.

There, median overall survival was 22.0 months with pembrolizumab and 10.7 months without, hazard ratio 0.56 (95% CI 0.45 to 0.70). Median time before the cancer grew was 9.0 months against 4.9 months, hazard ratio 0.48 (95% CI 0.40 to 0.58).

What made this the default first treatment

Before KEYNOTE-189, immune drugs were reserved for tumors with high PD-L1. This trial found the benefit held across PD-L1 levels in this group of patients. That is why chemotherapy plus pembrolizumab became the usual first treatment for most non-squamous lung cancers without a targetable gene change.

What this report cannot tell you

• People on the placebo arm could switch to pembrolizumab when their cancer grew. The true gap against never receiving it may be wider than measured.
• The later reports were follow-up updates. No new statistical threshold was set for them, so they describe rather than test.
• Anyone with an EGFR or ALK change was excluded. None of this applies to them.
• The 57 people who finished all 35 cycles were the ones doing well enough to get there. Their figures are not a forecast for anyone starting out.

Questions about first treatment for lung cancer

• Has my tumor been tested for EGFR, ALK and other targetable changes?
• What is my PD-L1 score, and does it change the plan here?
• How long would treatment continue if it is working?
• Which side effects of immune treatment should I report straight away?

Sources

This article was written from the sources below, which were checked on the source-check date shown above.

• JCO: KEYNOTE-189 5-year outcomes (phase 3) (primary)
• JCO: Updated analysis from KEYNOTE-189 (median follow-up 23.1 months) (primary)

How this article was prepared

Prepared by Cancer Explained's AI-assisted editorial system and checked against the sources listed below. This article has not been reviewed by a healthcare professional unless a named reviewer is specifically shown.

Cancer Explained is published by the National Cancer Information Foundation as a nonprofit-oriented public-interest education project. It is not a diagnostic service, does not recommend treatments, and is not for emergencies.

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