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CheckMate 227 showed that a chemotherapy-free pair of immunotherapy drugs, nivolumab and ipilimumab, helped people with advanced lung cancer live longer than chemotherapy alone, which made it a first-line option for tumours with any PD-L1 expression.
CheckMate 227 was a large open-label phase 3 programme in previously untreated advanced non-small-cell lung cancer without EGFR or ALK alterations. Part 1 randomised patients by PD-L1 status to nivolumab plus low-dose ipilimumab, nivolumab alone or nivolumab plus chemotherapy (PD-L1 of 1 percent or more), or to nivolumab plus ipilimumab or nivolumab plus chemotherapy (PD-L1 below 1 percent), each against platinum doublet chemotherapy. The co-primary endpoints were progression-free survival in tumours with high mutational burden and overall survival in PD-L1-positive tumours.
Nivolumab plus ipilimumab lengthened overall survival compared with chemotherapy in patients whose tumours expressed PD-L1 at 1 percent or more, and the benefit also appeared in the PD-L1-negative group. The tumour mutational burden endpoint did not translate into an overall survival difference. The combination was approved in the United States in May 2020 for PD-L1-positive disease, and the long-term follow-up has shown a tail of durable survivors in both PD-L1 groups.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
2,747 enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Overall survival, PD-L1 >=1%primary | Nivolumab + ipilimumab | - | 17.1 months | - | 0.007 | link |
| Chemotherapy | - | 14.9 months | ||||
| Overall survival at 2 years, PD-L1 >=1% | Nivolumab + ipilimumab | - | 40% | - | - | link |
| Chemotherapy | - | 32.8% | ||||
| Overall survival, PD-L1 <1% | Nivolumab + ipilimumab | - | 17.2 months | - | - | link |
| Chemotherapy | - | 12.2 months | ||||
| Overall survival, all randomised patients | Nivolumab + ipilimumab | - | 17.1 months | - | - | link |
| Chemotherapy | - | 13.9 months | ||||
| Duration of response, PD-L1 >=1% | Nivolumab + ipilimumab | - | 23.2 months | - | - | link |
| Chemotherapy | - | 6.2 months | ||||
| Grade 3-4 treatment-related adverse events | Nivolumab + ipilimumab | - | 32.8% | - | - | link |
| Chemotherapy | - | 36% |
A second publication from the CheckMate 227 trial, later than the first and described in its title as an update or longer-term analysis. Read it with the primary publication linked from the trial page; the record was linked automatically and its figures have not been checked by hand.
This is the paper Europe PMC returns for registry id NCT02477826 with the most citations, so it is the natural first reading for anyone following the CheckMate 227 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
Shares Extended-interval immunotherapy: give checkpoint inhibitors every 8-12 weeks once stable, Give immunotherapy in the morning, Randomised trials of stopping immunotherapy after one year versus continuing, Microbiome transplant as a routine immunotherapy adjunct and the tag subtype-trials.
Shares Ipilimumab, Bristol Myers Squibb, Nivolumab, Immune checkpoint inhibitors and the tag subtype-trials.
Shares Bristol Myers Squibb, Nivolumab, Immune checkpoint inhibitors and the tag subtype-trials.
Shares Bristol Myers Squibb, Nivolumab, Immune checkpoint inhibitors and the tag subtype-trials.
Shares PD-L1-high non-small-cell lung cancer without a driver mutation, Lung cancer (all types), Immune checkpoint inhibitors, Non-small-cell lung cancer and the tag subtype-trials.
Shares Lung cancer (all types), Immune checkpoint inhibitors, Non-small-cell lung cancer and the tag subtype-trials.
Shares Lung cancer (all types), Non-small-cell lung cancer and the tag subtype-trials.
Shares Lung cancer (all types), Non-small-cell lung cancer and the tag subtype-trials.