Nivolumab/Ipilimumab Continues to Show OS Benefit in NSCLC at 6 Years

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First-line immunotherapy with the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) maintains durable efficacy vs chemotherapy in patients with metastatic non–small cell lung cancer (NSCLC), regardless of PD-L1 expression, according to 6-year follow-up data from CheckMate 227 (NCT02477826).¹

Results from an updated analysis were recently reported at the 2023 World Conference on Lung Cancer (WCLC 2023), showing that with a minimum of 73.5 months of follow-up, nivolumab combined with ipilimumab continued to provide a benefit in overall survival (OS) in both patient groups, consisting of those with treatment-naive stage IV or recurrent NSCLC with no known EGFR/ALK alterations.

Among patients with PD-L1 ≥1% disease, the median OS was 17.1 months when treated with the combination vs 14.9 months among those given chemotherapy alone (HR, 0.78; 95% CI, 0.67-0.91). At 6 years, OS rates were 22% and 13% for the combination vs chemotherapy groups.

For those with PD-L1 <1%, the median OS observed was 17.4 months when given the combination of nivolumab plus ipilimumab vs 12.2 months for chemotherapy (HR, 0.65; 95% CI, 0.52-0.81). The 6-year OS rate with the combination was 16% compared with 5% for chemotherapy.

"Immunotherapy has transformed the treatment of advanced lung cancer, and thankfully, a diagnosis no longer means the same thing as it used to for many patients. With these 6-year results, we are seeing remarkably sustained and durable clinical survival benefits with nivolumab plus ipilimumab year-over-year," said Solange Peters, MD, PhD, professor and chair of medical oncology and the thoracic malignancies program in the Department of Oncology at the University Hospital of Lausanne in Lausanne, Switzerland.

To date, the combination of nivolumab and ipilimumab have shown significant improvements in OS in 6 phase 3 clinical trials across 5 tumor types, including metastatic NSCLC, metastatic melanoma, advanced renal cell carcinoma, malignant pleural mesothelioma, and esophageal squamous cell carcinoma.

In part 1 of the CheckMate 227 study, adult patients with treatment-naive stage IV or recurrent NSCLC with no known EGFR/ALK alterations were enrolled. For patients with tumor PD-L1 ≥1%, they were treated with either nivolumab plus ipilimumab, nivolumab monotherapy, or chemotherapy, while patients with tumor PD-L1 <1% were randomly assigned to receive nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy.²

The primary end points in part of the trial were OS in patients whose tumors express PD-L1 and PFS in patients with tumor mutational burden ≥10 mutations/megabase (mut/Mb) across the PD-L1 spectrum.

The previously-reported, 5-year landmark analysis from CheckMate 227 part 1 showed overall survival (OS) rates of 24% with nivolumab plus ipilimumab, compared with 14% with chemotherapy among patients with PD-L1 ≥1%. Among patients with PD-L1 <1%, OS rates were 19% versus 7%, respectively.¹

Additionally, 27% of patients with PD-L1 ≥1% disease treated with nivolumab plus ipilimumab who responded continued to have a response compared with 4% of patients given chemotherapy. The median duration of response (DOR) was higher in the combination arm at 24.5 months vs 6.7 months with chemotherapy, and progression-free survival (PFS) rates were 11% vs 2%.

In patients with PD-L1 <1%, 25% of patients given nivolumab and ipilimumab who responded were still in response vs no patients assigned chemotherapy at 6 years. The median DOR was 19.4 months for the combination and 4.8 months with chemotherapy. The 6-year PFS rate for this group of patients was 8% with nivolumab plus ipilimumab vs no patients receiving chemotherapy.

Between groups, approximately 50% of patients alive at 6 years were disease-free, and this analysis also showed that baseline health-related quality of life correlated with improved OS between arms.

There were no new safety signals identified and treatment was manageable. No differences were observed in the safety profile compared with previous reports from the trial.

"The long-term efficacy seen with the dual immunotherapy regimen in CheckMate-227 reinforce the importance of nivolumab plus ipilimumab to transform outcomes for appropriate patients with metastatic non–small cell lung cancer,” added Peters.

REFERENCES:

1. Six-year outcomes from phase 3 CheckMate -227 trial show durable, long-term survival with opdivo (nivolumab) plus yervoy (ipilimumab) in the first-line treatment of patients with metastatic non-small cell lung cancer. News release. Bristol Myers Squibb. September 11, 2023. Accessed September 15, 2023. https://tinyurl.com/532a696y

2. An investigational immuno-therapy trial of nivolumab, or nivolumab plus ipilimumab, or nivolumab plus platinum-doublet chemotherapy, compared to platinum doublet chemotherapy in patients with stage IV non-small cell lung cancer (NSCLC) (CheckMate 227). ClinicalTrials.gov. Updated September 13, 2023. Accessed September 15, 2023. https://www.clinicaltrials.gov/study/NCT02477826