Highlights from

World Conference on Lung Cancer

19th annual meeting

Toronto, Canada 23-26 September 2018

PD-L1 expression in untreated EGFR-mutant non-small-cell lung cancer and response to osimertinib

Prof. Suresh Ramalingam (Emory University School of Medicine, Winship Cancer Institute, USA) presented data on PD-L1 expression in untreated EGFR-mutant (EGFRm) advanced NSCLC. He also discussed response to osimertinib compared with standard EGFR tyrosine kinase inhibitors (TKIs) in the phase 3 FLAURA trial [1]. “Where does immunotherapy fit in patients with EGFR mutations and other driver events?” asked Prof. Ramalingam. “This is a key, clinically important question.”

Osimertinib is an oral, third-generation, CNS-active EGFR TKI that potently and selectively inhibits both EGFR TKI sensitising and EGFR T790M resistance mutations [1-5]. “The benefit of EGFR TKIs in treatment-naïve, EGFRm, PD-L1 positive patients is of high clinical interest,” Prof. Ramalingam said. A recent study of pembrolizumab in EGFR TKI-naïve patients with EGFRm and PD-L1 positive-advanced NSCLC failed to demonstrate efficacy [6]. “It was halted early,” said Prof. Ramalingam.

However, the FLAURA trial showed that osimertinib significantly improved PFS compared to standard of care EGFR TKIs in patients with untreated Ex19de/L858R-positive (EGFRm) NSCLC [1].

Participants with locally advanced/metastatic NSCLC who were positive for EGFRm and PD-L1 were stratified by mutation type and race (Asian/non-Asian) before being randomised to treatment. Exploratory endpoints included measurement of PD-L1 expression in freshly sectioned archival tumour tissue samples and assessment of clinical outcome by PD-L1 expression. Samples with tumour cell (TC) staining ≥1% were defined as PD-L1 expressers.

PD-L1 expression was lower in EGFRm-positive samples than in EGRFm-negative ones. It was also uncommon at higher thresholds (TC≥25% or TC≥50%) in EGRFm-positive samples. There were no progression-free survival (PFS) assessments in patients randomised to treatment with PD-L1 TC≥25% or TC≥50% tumours; there were too few of them to perform the analysis.

Patients who received osimertinib showed PFS benefit regardless of PD-L1 expression (Figure 6). According to Prof. Ramalingam, these outcomes support the following conclusions:

  • EGFRm testing is critical prior to treatment initiation in all patients with advanced NSCLC; and
  • osimertinib should be used as first-line treatment of patients with EGFRm advanced NSCLC, regardless of PD-L1 status.

[Figure 6] Patients received PFS benefit from osimertinib, regardless of PD-L1 expression [1] Osimertinib vs standard of care, PD-L1 expressers (TC≥1%)

WCLC 2018: Figure 6 FIRST Osimertinib vs standard of care, PD-L1 expressers

WCLC 2018: Figure 6 SECOND Osimertinib vs standard of care, PD-L1 negative

WCLC 2018: Figure 6 THIRD Osimertinib vs standard of care, PD-L1 unknown

  1. Soria JC, et al. N Engl J Med 2018;378:113-125.
  2. Cross DA, et al. Cancer Discov 2014;4:1046-1061.
  3. Mok TS, et al. GN Engl J Med 2017;376:629-640.
  4. Wu YL, et al. J Clin Oncol 2018:JCO2018777326.
  5. Reungwetwattana T, et al. J Clin Oncol 2018:JCO2018783118.
  6. Lisberg A, et al. J Thorac Oncol 2018;13:1138-1145.

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The content and interpretation of these conference highlights are the views and comments of the speakers/authors.