medwireNews: KEYNOTE-021 results indicate that adding pembrolizumab to carboplatin and pemetrexed chemotherapy could be an effective strategy for the first-line treatment of advanced, non-squamous non-small-cell lung cancer (NSCLC).
The phase II open-label trial findings were simultaneously reported at the ESMO 2016 annual meeting in Copenhagen, Denmark, and published online in The Lancet Oncology.
A RECIST objective response occurred in 55% of the 60 patients who were randomly assigned to receive four cycles of pembrolizumab 200 mg plus carboplatin to an area under the curve of 5 mg/mL per minute plus pemetrexed 500 mg/m2 every 3 weeks, followed by 2 years of pembrolizumab and indefinite pemetrexed maintenance.
By comparison, just 29% of the 63 patients who received the chemotherapy alone achieved an objective response, giving a significant estimated treatment difference of 26%, reported lead investigator Corey Langer, from the University of Pennsylvania in Philadelphia, USA.
Response occurred after a median of 1.5 months with the additional pembrolizumab versus 2.7 months with chemotherapy alone, and both responses were “durable”, with a respective 88% and 78% of responders in each group still alive and progression-free at the time of data cutoff.
The patients receiving pembrolizumab plus chemotherapy, who all had stage IIIB/IV disease and no EGFR or ALK targetable mutations, were stratified into two groups according to a programmed death-ligand 1 (PD-L1) tumour proportion score, with 21 scoring less than 1% and 39 at least 1%. There was no difference in the proportion who achieved an objective response, at 57% and 54%, respectively.
But further analysis of patients with a score greater than 1% showed that the rate of response in the pembrolizumab group varied from 26% among the patients with a score of 1–49% to 80% among those with a score of 50% or greater.
By contrast, among patients who received chemotherapy alone, the response rates for those with PD-L1 scores <1%, 1–49% and 50% or above were 13%, 39% and 35%, respectively.
However, the researchers say that the small patient numbers in the PD-L1 subgroups means that “it is not possible to conclusively determine whether there is a relationship between PD-L1 expression and efficacy in patients treated with pembrolizumab plus chemotherapy”.
Median progression-free survival was significantly longer for the patients given pembrolizumab plus chemotherapy versus chemotherapy alone, at 13.0 versus 8.9 months and an HR of 0.53.
“Although caution must be used in view of the relatively short follow-up duration and the amount of censoring noted after 6 months, to the best of our knowledge, this makes KEYNOTE-021 one of the first randomised, controlled studies of first-line chemotherapy for advanced NSCLC in which median progression-free survival exceeded 1 year”, Langer et al say.
The safety and efficacy of the addition of pembrolizumab to first-line platinum-based chemotherapy for advanced non-squamous NSCLC is now being further assessed in the two double-blind trials KEYNOTE-189 and KEYNOTE-047, the researchers add.
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