Five-Year Survival Outcomes of First-Line Nivolumab plus Ipilimumab versus Chemotherapy in Metastatic NSCLC: CheckMate 227

The CheckMate 227 part 1 trial (NCT02477826) demonstrated that first-line nivolumab plus ipilimumab is more effective than platinum-doublet chemotherapy in patients with metastatic non–small-cell lung cancer (NSCLC) regardless of tumor PD-L1 expression level.1 The combination treatment resulted in long-term, durable survival benefits. In a late-breaking presentation at the 2022 American Society of Clinical Oncology Annual Meeting, Brahmer and colleagues reported the results of the 5-year follow-up of CheckMate 227.2

CheckMate 227 enrolled patients with previously untreated stage IV or recurrent NSCLC, with no known EGFR/ALK mutations and an Eastern Cooperative Oncology Group performance status of 0 or 1.2 Patients with a PD-L1 expression level of ≥1% were randomized in a 1:1:1 ratio to receive nivolumab (3 mg/kg every 2 weeks) plus ipilimumab (1 mg/kg every 6 weeks), nivolumab (240 mg every 2 weeks), or platinum-doublet chemotherapy. Patients with tumor PD-L1 <1% were randomized 1:1:1 to receive nivolumab plus ipilimumab, nivolumab (360 mg every 3 weeks) plus chemotherapy, or chemotherapy alone.2

Patients were treated until progression, toxicity, or ≤2 years with immunotherapy. The investigators assessed overall survival (OS), progression-free survival, objective response rate, duration of response, and a novel efficacy end point, treatment-free interval.2 The treatment-free interval was evaluated in patients who discontinued study therapy for any reason, including treatment completion. It was defined as the time from the last study dose to the start of subsequent systemic treatment or death, whichever occurred first.2

At a minimum follow-up of 61.3 months, patients with tumor PD-L1 ≥1% (n = 1189) continued to derive long-term OS benefits with nivolumab plus ipilimumab compared with chemotherapy (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.66-0.91). The 5-year OS rates were 24% for patients in the nivolumab plus ipilimumab arm versus 17% for the nivolumab arm and 14% for the chemotherapy group.2 Patients in the nivolumab plus ipilimumab group had a median OS of 17.1 months compared with 15.7 months and 14.9 months for the nivolumab and chemotherapy arms, respectively.2

Similarly, patients with tumor PD-L1 <1% (n = 550) continued to derive OS benefit from nivolumab plus ipilimumab treatment compared with chemotherapy (HR, 0.65; 95% CI, 0.52-0.81). The 5-year OS rates were 19% for nivolumab plus ipilimumab, 10% for nivolumab plus chemotherapy, and 7% for chemotherapy alone. Patients in the nivolumab plus ipilimumab arm had a median OS of 17.4 months compared with 15.2 months and 12.2 months for the nivolumab and chemotherapy arms, respectively.2

Moreover, the median duration of response among patients treated with nivolumab plus ipilimumab was 24.5 months compared with 6.7 months for the chemotherapy group (PD-L1 ≥1%) and 19.4 months for the nivolumab plus ipilimumab group compared with 4.8 months for the chemotherapy group (PD-L1 <1%).2 Nivolumab plus ipilimumab increased the 5-year survivorship regardless of PD-L1 expression level, and the responses lasted ≥5 years in more than 40% of patients who responded. Furthermore, most responders remained treatment-free for ≥3 years after discontinuation of treatment.2

In summary, the 5-year follow-up of CheckMate 227 demonstrated that nivolumab plus ipilimumab is an effective and durable treatment regimen for patients with metastatic NSCLC, regardless of PD-L1 expression and is effective even in PD-L1–negative patients.


  1. Hellmann MD, Paz-Ares L, Bernabe Caro R, et al. Nivolumab plus ipilimumab in advanced non-small-cell lung cancer. N Engl J Med. 2019;381:2020-2031.
  2. Brahmer JR, Lee JS, Ciuleanu TE, et al. Five-year survival outcomes with nivolumab (NIVO) plus ipilimumab (IPI) versus chemotherapy (chemo) as first-line (1L) treatment for metastatic non–small cell lung cancer (NSCLC): results from CheckMate 227. Presented at: 2022 American Society of Clinical Oncology Annual Meeting; June 3-7, 2022; Chicago, IL. Abstract LBA9025.

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