As reported in the Journal of Clinical Oncology by Julie R. Brahmer, MD, MSc, FASCO, and colleagues, a 5-year analysis of the phase III CheckMate 227 trial showed improvement in overall survival with first-line nivolumab/ipilimumab vs platinum-doublet chemotherapy, at ≥ 3 years after cessation of study immunotherapy, in patients with metastatic non–small cell lung cancer (NSCLC) without EGFR or ALK aberrations.
The trial supported the May 2020 approval of the combination as a first-line treatment of patients with metastatic NSCLC with tumor PD-L1 expression of ≥1% with no EGFR or ALK genomic tumor aberrations.
Julie R. Brahmer, MD, MSc, FASCO
As stated by the investigators, the trial met its two primary endpoints in showing that the combination therapy prolonged progression-free survival in patients with high tumor mutational burden and overall survival in those with PD-L1 expression ≥ 1% vs chemotherapy; a prespecified descriptive analysis showed pronged overall survival with the combination in patients with PD-L1 < 1%.
Study Details
In the open-label trial, patients with tumor PD-L1 ≥ 1% (n = 1,739) were randomly assigned to receive nivolumab/ipilimumab, nivolumab alone, or platinum-doublet chemotherapy; patients with PD-L1 < 1% were randomly assigned to receive nivolumab/ipilimumab, nivolumab plus chemotherapy, or chemotherapy. Data are shown only for comparisons between the nivolumab/ipilimumab vs chemotherapy alone groups.
Key Findings
At a minimum follow-up of 61.3 months, 5-year overall survival was 24% in the nivolumab/ipilimumab group vs 14% in the chemotherapy group among patients with PD-L1 ≥ 1% (hazard ratio [HR] = 0.77, 95% confidence interval [CI] = 0.66–0.91) and 19% vs 7% among patients with PD-L1 < 1% (HR = 0.65, 95% CI = 0.52–0.81).
Median durations of response were 24.5 vs 6.7 months among patients with PD-L1 ≥ 1%, with 28% vs 3% of responses lasting ≥ 5 years, and 19.4 vs 4.8 months among those with PD-L1 < 1%, with 21% vs 13% of responses lasting ≥ 5 years.
Among patients surviving for 5 years, 66% of those with PD-L1 ≥ 1% and 64% of those with PD-L1 < 1% were off nivolumab/ipilimumab without initiating subsequent systemic anticancer therapy.
Among patients discontinuing all study drugs due to treatment-related adverse events, 5-year overall survival rates for the PD-L1 ≥ 1% and PD-L1 < 1% populations combined were 39% among 97 patients who received nivolumab/ipilimumab (median treatment duration = 3.7 months) vs 20% among 48 who received chemotherapy alone (median treatment duration = 2.5 months).
Among patients who received nivolumab/ipilimumab who survived for ≥ 5 years, quality of life measured at 5 years using the EQ-5D visual analog scale showed that scores improved from baseline and then remained at or above the norm for the general U.S. population.
No new safety signals were identified.
The investigators concluded, “With all patients off immunotherapy treatment for ≥ 3 years, nivolumab plus ipilimumab increased 5-year survivorship vs chemotherapy, including long-term, durable clinical benefit, regardless of tumor PD-L1 expression. These data support nivolumab plus ipilimumab as an effective first-line treatment for patients with metastatic NSCLC.”
Dr. Brahmer, of Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Bristol Myers Squibb. For full disclosures of the study authors, visit ascopubs.org.
