Very high PD-L1 expression increases pembrolizumab benefit in NSCLC
medwireNews: Response is significantly and positively associated with PD-L1 expression in patients with non-small-cell lung cancer (NSCLC) receiving first-line pembrolizumab, suggest the results of a retrospective analysis.
“[C]linical outcomes are improved with increasing PD-L1 expression levels ≥75% and particularly ≥90[%],” report Mark Awad (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) and colleagues in the Annals of Oncology.
The researchers gathered data on patients with advanced, EGFR/ALK alteration-negative NSCLC with a PD-L1 expression level of 50% or more who were treated with at least one dose of first-line pembrolizumab monotherapy at one of four US academic centers.
In the full cohort of 187 patients, the overall response rate (ORR) was 44.4%; median progression-free survival (PFS) was 6.5 months and median overall survival (OS) was not reached over a median follow-up of 12.6 months.
However, when the researchers focused on the 80 patients with a PD-L1 expression level of 90–100%, they found an ORR of 60.0% – significantly higher than the 32.7% rate among the 107 individuals with PD-L1 expression of 50–89%.
Similarly, median PFS was significantly longer in the 90–100% than the 50–89% group, at 14.5 versus 4.1 months, as was median OS, at not reached versus 15.9 months. And after adjustment for ECOG performance status, the higher PD-L1 level was significantly associated with improved PFS and OS, with hazard ratios of 0.50 and 0.39, respectively.
The team also examined clinical outcomes by increasing PD-L1 expression quartiles of 75–100% (59.9%) versus 50–74% (40.1% of the overall cohort). ORR and median PFS were both significantly better in the higher PD-L1 expression group, at 53.6% versus 30.7%, and 7.8 versus 4.3 months (adjusted HR=0.63), respectively. By contrast, median OS did not significantly differ in the two groups, at not reached versus 20.3 months (adjusted HR=0.62).
The question of whether to use pembrolizumab as monotherapy or combined with chemotherapy in NSCLC patients with a PD-L1 level of at least 50% is currently unresolved, say the researchers. However, they suggest, the current results indicate that those with very high PD-L1 expression levels might be “well-suited” for treatment with pembrolizumab monotherapy.
“Additional analyses from completed first-line immunotherapy clinical trials of outcomes in patients with NSCLC and PD-L1 expression levels ≥75% and ≥90% may help to validate [these] findings,” the team concludes.
By Catherine Booth
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