CheckMate 227: 5-year survival outcomes support efficacy of nivolumab plus ipilimumab
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CHICAGO — Among previously untreated patients with metastatic non-small cell lung cancer, nivolumab plus ipilimumab provided durable, long-term clinical benefit at 5-year follow-up compared with chemotherapy.
The researchers say the data from CheckMate227 presented at ASCO Annual Meeting is the longest reported follow-up from any phase III trial evaluating an immunotherapy plus immunotherapy combination.
“First-line treatment of metastatic non-small cell lung cancer with nivolumab and ipilimumab was investigated in CheckMate 227 Part 1,” Julie R. Brahmer, MD, co-director of the upper aerodigestive department within Bloomberg-Kimmel Institute for Cancer Immunotherapy and professor of oncology at Johns Hopkins University, said during the presentation. “Long-term and durable survival benefit vs. platinum doublet chemotherapy was previously reported regardless of tumor PD-L1 expression level. As a reminder PD-L1 greater than or equal to 1% is the primary endpoint population for this study.”
The trial included patients with previously untreated stage IV or recurrent NSCLC with no known EGFR or ALK alterations and an ECOG performance status of 1 or less. The minimum follow-up was 61.3 months. Patients with a PD-L1 expression of 1% or greater (n = 1,189) were randomized to receive combination nivolumab and ipilimumab, nivolumab alone, or chemotherapy alone, while patients with a PD-L1 expression of less than 1% (n = 550) were randomized to receive combination nivolumab (Opdivo, Bristol Myers Squibb) and ipilimumab (Yervoy, Bristol Myers Squibb), nivolumab with chemotherapy, or chemotherapy alone.
According to the abstract, the study assessments included OS, PFS, objective response rate, duration of response and treatment-free interval. Treatment-free interval was measured as patients who discontinued study therapy for any reason, including treatment completion, and was defined as the time from last study dose to start of subsequent systemic therapy or death.
In patients with a PD-L1 expression of 1% or greater, nivolumab and ipilimumab demonstrated continued long-term OS benefit compared with chemotherapy alone (HR = 0.77; [95% CI, 0.66–0.91]). Moreover, the 5-year OS rate for nivolumab and ipilimumab was 24% compared with 17% for nivolumab alone, and 14% for chemotherapy alone.
Similarly, in patients with a PD-L1 expression of less than 1%, nivolumab and ipilimumab also demonstrated continued long-term OS benefit when compared with chemotherapy (HR = 0.65; [95% CI, 0.52–0.81]). The 5-year OS rates were 19% for nivolumab and ipilimumab, 10% for nivolumab and chemotherapy, and 7% for chemotherapy alone.
“Consistent with data discussed from the PD-L1 positive population, long-term durable outcomes are observed with nivolumab and ipilimumab in patients with PD-L1-negative disease from both a PFS and duration of response perspective,” Brahmer said. “In patients that survive 5 years, improved outcomes were universally observed with nivolumab and ipilimumab vs. chemotherapy, irrespective of PD-L1 expression.”
At 5 years, 66% of patients in the nivolumab and ipilimumab group who had a PD-L1 expression of 1% or greater remained treatment free 3 years or more after discontinuing the study therapy. For patients in the same group with a PD-L1 expression of less than 1%, 64% were treatment free for 3 years or more after discontinuing the study therapy at 5-year follow-up.
“Nivolumab and ipilimumab led to increased 5-year survivorship. Among these 5-year survivors and regardless of PD-L1 expression level, responses were maintained for greater than 5 years in more than 40% of those who responded. The majority remain treatment free for more than 3 years after treatment discontinuation. Quality of life was similar to the general U.S. population,” Brahmer concluded. “These long-term results from CheckMate 227 further support nivolumab and ipilimumab as an effective first-line treatment for patients with metastatic non-small cell lung cancer regardless of tumor PD-L1 expression level.”
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Brahmer JR, et al. Abstract LBA9025. Presented at: ASCO Annual Meeting, June 3-7, 2022, Chicago.
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