The combination of nivolumab and ipilimumab continues to offer a long-term, durable efficacy benefit for metastatic non-small cell lung cancer patients compared with chemotherapy, according to the 6-year update from CheckMate 227 Part 1 (NCT02477826). This research, which was presented during the International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer 2023 in Singapore, is the longest follow-up across first-line immunotherapy clinical trials in this patient population, according to the study authors.
"Our findings represent a pivotal moment in the management of metastatic NSCLC. The extended survival and enhanced quality of life observed with nivolumab + ipilimumab underscore the potential for a paradigm shift in treatment strategies," said study author 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 Switzerland.
"The evidence we present offers a compelling case for the transformative potential of nivolumab plus ipilimumab in metastatic non-small cell lung cancer treatment. Our findings underscore the significance of personalized care and better outcomes for patients," she noted.
Background & Design
Nivolumab plus ipilimumab has demonstrated long-term, durable survival benefit in several metastatic solid tumors, including NSCLC, according to Peters. "In the landmark 5-year analysis of the Phase III CheckMate 227 Part 1 study, first-line nivolumab plus ipilimumab continued to provide long-term, durable survival benefit versus chemotherapy and led to an increased 5-year survivorship in patients with metastatic NSCLC, regardless of tumor PD-L1 expression."
For this clinical trial, eligible patients included adults with treatment-naive Stage IV or recurrent NSCLC, no known EGFR/ALK alterations, and ECOG performance status <=1. Patients were divided into cohorts based on tumor PD-L1 expression levels.
Patients with tumor PD-L1 >=1 percent (Part 1a; 1,189 patients) were randomized (1:1:1) to nivolumab plus ipilimumab (396 patients), nivolumab (396 patients), or chemotherapy (397 patients). Patients with tumor PD-L1 <1 percent (Part 1b, 550 patients) were randomized (1:1:1) to nivolumab plus ipilimumab (187 patients), nivolumab plus chemotherapy (177 patients), or chemotherapy (186 patients).
Independent primary endpoints included progression-free survival in patients with tumor mutational burden >=10 mutations/megabase and overall survival among patients whose tumors expressed PD-L1. Exploratory analyses included overall survival by response and tumor burden expression, as well as overall survival by baseline health-related quality of life. At IASLC 2023, Peters and colleagues reported updated outcomes with a minimum follow-up of 6 years.
Key Findings
With a minimum follow-up of 73.4 months, data from CheckMate 227 Part 1 confirms the continued survival benefits associated with nivolumab plus ipilimumab versus chemotherapy.
The 6-year overall survival rates were significantly higher among patients who received the combination treatment when compared with chemotherapy at 22 percent versus 13 percent and 16 percent versus 5 percent, respectively, in patients with tumor PD-L1 >=1 percent or <1 percent.
Researchers observed consistent clinical benefit across additional efficacy endpoints, including objective response rates, duration of response, and quality of life regardless of tumor PD-L1 expression.
In patients with PD-L1 >=1 percent disease, Peters reported that 27 percent of patients treated with nivolumab plus ipilimumab versus 4 percent in the chemotherapy group continued to have a response. Data showed that 25 percent of patients with PD-L1 <1 percent in the combination cohort were still responding at 6 years versus no patients in the chemotherapy arm. Six-year progression-free survival rates for nivolumab plus ipilimumab versus chemotherapy were as follows: 11 percent versus 2 percent (PD-L1 >=1%) and 8 percent versus NA (PD-L1 <1%), according to Peters. The researchers also examined patients who completed health-related quality-of-life assessments with at least 5 years (61.3 months) of follow-up.
"Higher baseline EQ-5D-3L UI scores were positively associated with overall survival," reported Peters. "Median overall survival with nivolumab plus ipilimumab was 21.7 (high score) versus 12.8 months (low score). Median overall survival with chemotherapy was 17.5 versus 10.0 months, respectively."
Data revealed no new safety signals and treatment was manageable, according to the researchers. They observed no differences in the safety profile compared with previous CheckMate 227 reports.
"Additional analyses complement other long-term outcomes data, further demonstrating the clinical benefits of nivolumab plus ipilimumab," Peters concluded, during a press briefing presentation. "These data represent the longest reported follow-up across Phase III studies of first-line immunotherapy in patients with metastatic NSCLC. The clinical benefit is further highlighted as an effective treatment, regardless of the level of PD-L1."
Catlin Nalley is a contributing writer.