KEYNOTE-024 demonstrates pembrolizumab superiority for PD-L1-positive NSCLC
medwireNews: Pembrolizumab is superior to platinum-based chemotherapy for the first-line treatment of advanced non-small-cell lung cancer (NSCLC) expressing programmed death-ligand 1 (PD-L1) in at least 50% of cells, KEYNOTE-024 results show.
The phase III open-label study findings for patients with stage IV NSCLC were reported at the ESMO 2016 Congress, held in Copenhagen, Denmark, and published simultaneously in The New England Journal of Medicine.
In all, 154 treatment-naïve patients without an activating EGFR mutation or ALK translocation were randomly assigned to receive pembrolizumab 200 mg every 3 weeks and 151 patients were given 4–6 cycles of an investigator’s choice of combination platinum-based chemotherapy.
The primary endpoint of median progression-free survival (PFS) was significantly longer with pembrolizumab treatment than chemotherapy, at 10.3 versus 6.0 months and a hazard ratio (HR) for disease progression or death of 0.50.
Overall survival (OS) at 6 months was 80.2% with pembrolizumab and 72.4% with chemotherapy, with corresponding 12-month rates of 70.0% versus 54.0%. Median OS was not reached in either group at the time of the second interim analysis but the HR of 0.60 was significantly in favour of pembrolizumab.
Presenting author Martin Reck, from the German Center of Lung Research in Grosshansdorf, emphasized at a press conference that the PFS and OS benefits were both “consistent and improving over time”, and that the OS gain occurred despite approximately 50% of patients given chemotherapy crossing over to an anti-PD-L1 therapy.
Pembrolizumab was also associated with a significantly higher RECIST objective response rate than chemotherapy (44.8 vs 27.8%). Median duration of response was not reached in the pembrolizumab group and was 6.3 months for those given chemotherapy.
The side effect profile for pembrolizumab was “as expected”, Reck commented. Grade 3 or worse events occurred in 26% of patients who received pembrolizumab for a median of 7.0 months versus 53% of patients who received chemotherapy for a median of 3.5 months.
Serious adverse events occurred in 21% of both groups, leading to discontinuation in 7% and 11% of patients in the pembrolizumab and chemotherapy arms, respectively.
“Pembrolizumab may be a new standard of care for first-line therapy for advanced NSCLC that expresses high levels of PD-L1”, Reck therefore concluded.
And noting that around a third of NSCLC patients express PD-L1 in at least 50% of cells, he told the press conference that “the diagnostic work-up will completely change following these data, so that we have to look for the PD-L1 expression status upfront from today.”
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