medwireNews: Nivolumab does not offer a progression-free survival (PFS) advantage over chemotherapy as a first-line treatment for patients with stage IV or recurrent non-small-cell lung cancer (NSCLC) and a programmed death ligand 1 (PD-L1) expression level of 5% or more, phase III trial results indicate.
Contrary to previously reported data for the programmed cell death protein 1 (PD-1) inhibitor pembrolizumab, there was not even an increase in PFS with nivolumab among patients with a PD-L1 expression level of at least 50%, the researchers report. They caution, however, that this was not a prespecified analysis in the current trial – CheckMate 026 – and the number of patients with this level of expression was imbalanced, being fewer in the nivolumab treatment group than the chemotherapy arm.
Among patients with PD-L1 expression of 5% or above, the median PFS for the 211 participants receiving nivolumab (3 mg/kg body weight every 2 weeks) was 4.2 months, which was similar to the 5.9 months achieved by 212 patients receiving up to six cycles of platinum-based chemotherapy.
The 1-year PFS rate between the two groups also did not differ significantly, at 24% for those given the PD-1 inhibitor and 23% for the chemotherapy-treated group.
Overall survival was also comparable at a median 14.4 and 13.2 months with nivolumab and chemotherapy, respectively, with 1-year rates of 56% and 54%.
In addition, objective response rate was similar for nivolumab- and chemotherapy-treated patients, at a corresponding 26% and 33%, as was the median time to response, at 2.8 and 2.6 months.
The duration of response, however, was more than twice as long with nivolumab as with chemotherapy, at a median 12.1 versus 5.7 months.
The researchers, led by David Carbone (Ohio State University Comprehensive Cancer Center, Columbus, USA), note that the survival findings were similar when all 541 study participants with NSCLC and PD-L1 expression of 1% or above participating in the study were assessed and across most planned subgroup analyses.
One potential hypothesis-generating finding from these analyses arose among patients with a high tumor-mutation burden, involving 47 of those in the nivolumab group and 60 in the chemotherapy group. The response rate was higher with nivolumab than chemotherapy (47 vs 28%) and the median PFS was longer (9.7 vs 5.8 months), suggesting that immunotherapy may have “enhanced activity” in these patients, the researchers suggest in The New England Journal of Medicine.
But in a related editorial, Edward Garon (University of California, Los Angeles, USA), likens high tumor-mutation burden as a biomarker to “an algorithm developed today that predicts last season’s World Series victory by the Cubs. Although potentially meritorious, its ability to pick this season’s champion is unclear.”
He continues: “If subtly different PD-L1–enhancement strategies can distinguish a strongly positive study from a clearly negative one, it will be important to evaluate consistency across pathologists.
“If the strategies for the selection of patients in clinical practice differ significantly from proven approaches, the data suggest that our patients may not derive the same benefits as have been seen in clinical trials.”
Nivolumab had a favorable safety profile compared with chemotherapy with no new and unexpected safety signals. Treatment-related adverse events of grade 3 and 4 occurred in 18% of patients receiving nivolumab and 51% of those receiving chemotherapy.
By Lucy Piper
medwireNews is an independent medical news service provided by Springer Healthcare. © 2017 Springer Healthcare part of the Springer Nature group