medwireNews: CheckMate 227 shows that treatment with nivolumab plus ipilimumab significantly improves progression-free survival (PFS) compared with chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) and a high tumor mutational burden.
Speaking at a press conference at the American Association for Cancer Research Annual Meeting 2018 in Chicago, Illinois, USA, lead researcher Matthew Hellman (Memorial Sloan Kettering Cancer Center, New York, USA) described the findings as “practice changing.”
Furthermore, Hellman and co-authors write in The New England Journal of Medicine that the results “validate the role of nivolumab plus ipilimumab as an effective first-line therapy in NSCLC and tumor mutational burden as an important and independent biomarker in advanced NSCLC.”
The Checkmate 227 phase III trial consists of multiple parts that compare nivolumab plus ipilimumab with nivolumab monotherapy or nivolumab plus platinum-doublet chemotherapy (depending on PD-L1 expression level), and with chemotherapy alone. In total, 1739 patients with stage IV or recurrent NSCLC that was not previously treated with chemotherapy were included in the study.
The current analysis focuses on the co-primary endpoint of PFS in patients with a high tumor mutational burden (≥10 mutations per megabase) who were randomly assigned to receive treatment with nivolumab plus ipilimumab (n=139) or chemotherapy (n=160). These patients represent approximately 45% of those with NSCLC, Hellmann noted.
The researchers report that the risk for disease progression or death was a significant 42% lower at 1 year in the patients who received nivolumab plus ipilimumab than in those who received chemotherapy, with median PFS rates of 42.6% and 13.2%, respectively. Median PFS times were 7.2 and 5.5 months, respectively.
Moreover, the response was durable; 68% of responders to nivolumab plus ipilimumab had an ongoing response at 1 year, compared with 25% of those who responded to chemotherapy.
The objective response rate was 45.3% with nivolumab plus ipilimumab and 26.9% with chemotherapy.
The team also found that multivariate adjustment for baseline PD-L1 expression level (≥1 vs <1%), sex, squamous or nonsquamous histology, and ECOG performance status did not alter the findings.
By contrast, there was no significant difference in median PFS between the two treatments among patients with a low tumor mutational burden (<10 mutations per megabase), at 3.2 months with nivolumab plus ipilimumab and 5.5 months with chemotherapy.
Grade 3 or 4 treatment-related adverse events occurred at a similar rate in the patients who received nivolumab plus ipilimumab (31.2%) and in those who received chemotherapy (36.1%) and “were consistent with previously reported data on first-line treatment of NSCLC,” Hellmann et al remark.
Hellmann concluded: “The results show that in [tumor mutational burden]-high NSCLC patients, nivolumab plus ipilimumab provides improved benefit compared to chemotherapy, increases benefit compared to anti-PD-1 monotherapy, yields durable responses, spares the use of chemotherapy in the first-line setting, and could preserve an effective option in the second line of therapy, if needed.”
Analysis of data for the co-primary end point of overall survival among patients selected on the basis of PD-L1 expression level is ongoing.
By Laura Cowen
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