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Used just two cycles of chemotherapy to cover the first weeks while dual immunotherapy takes effect, an answer to the criticism that immunotherapy alone is too slow for people with heavy disease.
CheckMate 227 had shown that nivolumab with ipilimumab beats chemotherapy in the first line, but the survival curves cross early: patients with a large tumour burden can progress before dual checkpoint blockade works. CheckMate 9LA tested a limited course of chemotherapy as a bridge. It randomised 719 of 1,150 enrolled patients at 103 hospitals in 19 countries between August 2017 and January 2019 to nivolumab 360 mg every three weeks with ipilimumab 1 mg/kg every six weeks plus two cycles of platinum doublet chemotherapy (361), or to four cycles of chemotherapy alone (358), stratified by histology, sex and PD-L1 expression.
At the preplanned interim analysis with a median 9.7 months of follow-up, median overall survival was 14.1 months (95 percent confidence interval 13.2 to 16.2) against 10.7 months (9.5 to 12.4), hazard ratio 0.69 (96.71 percent confidence interval 0.55 to 0.87, p=0.00065). With 3.5 months more follow-up it was 15.6 months (13.9 to 20.0) against 10.9.
The FDA approved the regimen in 2020. England is the exception: NICE TA724 (8 September 2021) does not recommend nivolumab with ipilimumab and two cycles of platinum doublet chemotherapy for untreated metastatic disease, so the regimen is not routinely funded there even though it is a standard option in the United States and much of Europe.
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.
719 randomised.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Overall survivalprimary | Nivolumab, ipilimumab and two cycles of chemotherapy | 361 | 14.1 months | 0.69 (0.55 to 0.87) | 0.00065 | link |
| Four cycles of chemotherapy | 358 | 10.7 months |
Shares Tumour proportion score (TPS), Immune checkpoint, Adenocarcinoma of the lung, Bristol Myers Squibb.
Shares Ipilimumab, Pemetrexed, Bristol Myers Squibb, Paclitaxel / nab-paclitaxel.
Shares Tumour proportion score (TPS), Immune checkpoint, Squamous cell carcinoma of the lung, Bristol Myers Squibb.
Shares Pemetrexed, Bristol Myers Squibb, Nivolumab, Cisplatin.
Shares Ipilimumab, Pemetrexed, Nivolumab, Cisplatin.
Shares Pemetrexed, Paclitaxel / nab-paclitaxel, Cisplatin, Platinum agents.
Shares Immune checkpoint, Adenocarcinoma of the lung, Paclitaxel / nab-paclitaxel, Platinum agents.
Shares Immune checkpoint, Bristol Myers Squibb, Paclitaxel / nab-paclitaxel, Nivolumab.