In this large study, people with advanced non-small-cell lung cancer who had not had chemotherapy before received either a combination of two immunotherapy drugs (nivolumab and ipilimumab) or chemotherapy. Patients who received the immunotherapy combination typically lived longer, and this benefit was seen whether the level of the PD-L1 protein in the tumour was high or low. Responses to treatment also lasted longer in the immunotherapy group, and its serious side effects were no more common than with chemotherapy.
First line, without EGFR or ALK alterations
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Continuous | |||
| Nivolumab | 360 mg | IV, 30-minute infusion | Every 3 weeks |
| Ipilimumab | 1 mg/kg | IV, 30-minute infusion | Every 6 weeks |
On the page “Ipilimumab (Yervoy)” · Other cancers, with nivolumab (FDA label, revised 08/2026)
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Nivolumab 3 mg/kg IV over 30 minutes every 2 weeks + ipilimumab 1 mg/kg IV over 30 minutes every 6 weeks; until disease progression, unacceptable toxicity or a maximum of 2 years (24 months). Treatment beyond progression was allowed in clinically stable patients with clinical benefit; if the combination was stopped for an adverse event attributed to ipilimumab, nivolumab monotherapy could continue.
Nivolumab 240 mg (flat dose) IV every 2 weeks; until disease progression, unacceptable toxicity or a maximum of 2 years.
Platinum doublet chemotherapy every 3 weeks for 4 cycles, by histology:
As in the PD-L1 1% or more group: nivolumab 3 mg/kg IV over 30 minutes every 2 weeks + ipilimumab 1 mg/kg IV over 30 minutes every 6 weeks; until disease progression, unacceptable toxicity or a maximum of 2 years (24 months). Treatment beyond progression was allowed in clinically stable patients with clinical benefit; if the combination was stopped for an adverse event attributed to ipilimumab, nivolumab monotherapy could continue.
Nivolumab 360 mg IV every 3 weeks with platinum doublet chemotherapy every 3 weeks (regimen chosen by histology); nivolumab until progression, unacceptable toxicity or a maximum of 2 years. The chemotherapy doses and number of cycles for this arm are not stated separately in the sources reviewed.
Platinum doublet chemotherapy every 3 weeks by histology (pemetrexed–platinum regimens for non-squamous and gemcitabine–platinum for squamous disease; the exact doses in the FDA label refer to the chemotherapy arm of the PD-L1 1% or more group).
Source of the regimen details: Full text of the 5-year report of this trial (Brahmer et al., J Clin Oncol 2023; PMC9937094) for the nivolumab and ipilimumab doses in all arms and the 2-year maximum of immunotherapy; FDA label for Opdivo (DailyMed, section 14.5, CHECKMATE-227) for infusion durations, chemotherapy doses and the 4 cycles of chemotherapy. The full text of the NEJM 2019 paper was not available in PMC.
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Adults with histologically confirmed stage IV or recurrent NSCLC with no prior systemic therapy for advanced/metastatic disease, ECOG performance status 0 or 1, and no sensitising EGFR mutation or known ALK translocation. Exclusion criteria: untreated central nervous system metastases, carcinomatous meningitis, active autoimmune disease or need for systemic immunosuppression. Treated brain metastases were allowed if the patient had returned to neurological baseline at least 2 weeks before enrolment and was off corticosteroids or on a stable/decreasing dose of less than 10 mg prednisone (or equivalent) per day.
PD-L1 was measured centrally with the PD-L1 IHC 28-8 pharmDx assay, and patients with PD-L1 of 1% or more and less than 1% were randomised in two separate groups (each 1:1:1); stratified by histology (squamous vs non-squamous).
Primary endpoint reported in this paper: overall survival with nivolumab + ipilimumab compared with chemotherapy in patients with PD-L1 expression of 1% or more. Duration of response and overall survival in patients with PD-L1 below 1% and in all patients, as well as safety, were among the other reported findings.
In the overall study population, grade 3 or 4 treatment-related adverse events occurred in 32.8% of patients in the nivolumab + ipilimumab group and 36.0% in the chemotherapy group. According to the FDA label (576 patients on nivolumab + ipilimumab): serious adverse events 58%; discontinuation of nivolumab and ipilimumab due to adverse events 24% and interruption of at least one dose 53%; common serious adverse events (2% or more): pneumonia, diarrhoea/colitis, pneumonitis, hepatitis, pulmonary embolism, adrenal insufficiency and hypophysitis; fatal adverse events 1.7% (including pneumonitis in 4 patients, myocarditis and acute kidney injury). In the 5-year report, discontinuation of all drugs because of treatment-related adverse events occurred in 17% of the nivolumab + ipilimumab group and 8% of the chemotherapy group, and no new safety concerns emerged with longer follow-up.
This trial showed that nivolumab plus ipilimumab as first-line treatment in advanced NSCLC, independent of PD-L1 expression level, produces longer overall survival than chemotherapy, and no new safety concerns were reported with longer follow-up. The status of drug approvals and current clinical guideline recommendations (such as NCCN and ESMO) should be checked separately, as they are not mentioned in the abstract.
The trial is open-label. The reported primary endpoint covers only patients with PD-L1 of 1% or more, and the findings in the PD-L1 below 1% group and in all patients are reported descriptively in the abstract. Patient numbers are not given in the abstract (per the 5-year report, 1189 patients with PD-L1 of 1% or more; per the FDA label, 396 nivolumab + ipilimumab patients vs 397 chemotherapy patients in the primary comparison). Per protocol, immunotherapy continued for a maximum of 2 years.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.
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