LUNG CANCER Patients with very high PD-L1 expression (>90%) show particularly good response to PD-1 inhibition compared to lower expressing tumours.

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Dec. 9, 2019

SCIENTIFIC

LUNG CANCER: Patients with very high PD-L1 expression (>90%) show particularly good response to PD-1 inhibition, with ORR 60% and prolonged PFS & OS compared to lower expressing tumours.

 

"Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression"

E J Aguilar et al; Annals of Oncology, Volume 30, Issue 10, October 2019, Pages 1653–1659,

Background

In non-small-cell lung cancers with programmed death-ligand 1 (PD-L1) expression on ≥50% of tumor cells, first-line treatment with the PD-1 inhibitor pembrolizumab improves survival compared with platinum-doublet chemotherapy. Whether higher PD-L1 levels within the expression range of 50%–100% predict for even greater benefit to pembrolizumab is currently unknown.

Patients and methods

In this multicenter retrospective analysis, we analyzed the impact of PD-L1 expression levels on the overall response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) in patients who received commercial pembrolizumab as first-line treatment of non-small-cell lung cancer (NSCLC) with a PD-L1 expression of ≥50% and negative for genomic alterations in the EGFR and ALK genes .

Results

Among 187 patients included in this analysis, the ORR was 44.4% [95% confidence interval (CI) 37.1% to 51.8%], the mPFS was 6.5 months (95% CI 4.5–8.5), and the mOS was not reached. The median PD-L1 expression level among patients who experienced a response to pembrolizumab was significantly higher than among patients with stable or progressive disease (90% versus 75%, P < 0.001). Compared with patients with PD-L1 expression of 50%–89% (N = 107), patients with an expression level of 90%–100% (N = 80) had a significantly higher ORR (60.0% versus 32.7%, P < 0.001), a significantly longer mPFS [14.5 versus 4.1 months, hazard ratio (HR) 0.50 (95% CI 0.33–0.74), P < 0.01], and a significantly longer mOS [not reached versus 15.9 months, HR 0.39 (95% CI 0.21–0.70), P = 0.002].

Conclusion

Among patients with NSCLC and PD-L1 expression of ≥50% treated with first-line pembrolizumab, clinical outcomes are significantly improved in NSCLCs with a PD-L1 expression of ≥90%. These findings have implications for treatment selection as well as for clinical trial interpretation and design.