First-line pembrolizumab plus chemotherapy boosts advanced NSCLC outcomes
medwireNews: Adding pembrolizumab to standard chemotherapy significantly delays disease progression and improves overall survival (OS) in patients with previously untreated metastatic nonsquamous non-small-cell lung cancer (NSCLC), KEYNOTE-189 data show.
For the trial, the 616 patients, who all lacked sensitizing EGFR or ALK mutations and were not restricted by programmed death ligand 1 (PD-L1) expression level, were randomly assigned to receive treatment with pemetrexed and a platinum-based drug plus the PD-1 inhibitor pembrolizumab (n=410) or placebo (n=206).
Treatment was given every 3 weeks for four cycles, after which patients received pembrolizumab or placebo with pemetrexed maintenance therapy for a maximum of 35 cycles.
After a median follow-up period of 10.5 months, the estimated 1-year OS rate was significantly higher in the pembrolizumab-combination group than in the placebo-combination group, at 69.2% versus 49.4% with a corresponding hazard ratio (HR) for death of 0.49.
Writing in The New England Journal of Medicine, Leena Gandhi (New York University Langone Health, USA) and colleagues point out that pembrolizumab has replaced cytotoxic chemotherapy as the first-line treatment of choice for patients with a tumor proportion score for PD-L1 of 50% or greater, but only a minority of patients with NSCLC fall into this category.
It is therefore notable that the significant benefit of pembrolizumab was seen in all subgroups analysed, including across all PD-L1 tumor proportion categories (<1%, 1–49%, and ≥50%), where HRs ranged from 0.42 at the highest level of PD-L1 expression to 0.59 at the lowest level.
Median progression-free survival (PFS) was also significantly longer in the pembrolizumab-combination group than in the placebo-combination group, at 8.8 versus 4.9 months (HR=0.52), with an estimated 34.1% and 17.3%, respectively, alive and progression-free at 12 months.
In line with the OS data, the HRs for PFS were below 1.00 in favour of pembrolizumab use in all subgroups analyzed and across all categories of PD-L1 tumor proportion score, although they did not reach statistical significance for patients aged 65 years and older or for those with a PD-L1 proportion below 1%.
Gandhi and co-authors comment that “[t]he addition of pembrolizumab did not appear to increase the frequency of adverse events that are commonly associated with chemotherapy regimens involving pemetrexed and a platinum-based drug.”
Indeed the rate of grade 3 or higher adverse events was 67.2% among patients in the pembrolizumab-combination group and 65.8% among those in the placebo-combination group.
The researchers also point out that “the incidence of most immune-mediated adverse events was not higher with pembrolizumab-combination therapy than that previously observed with pembrolizumab monotherapy.”
Immune-mediated adverse events were recorded in 22.7% of patients in the pembrolizumab-combination group and in 11.9% of those in the placebo-combination group.
The study findings were also presented at the American Association for Cancer Research Annual Meeting 2018, held in Chicago, Illinois.
By Laura Cowen
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