Older age and low neutrophilia inflammation predictor for osimertinib efficacy

Osimertinib – a third generation irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) – has shown highly significant efficacy in non-small-cell lung cancer (NSCLC) patients with sensitive mutations as well as in patients with a T790M resistance mutation. EGFR T790M is a robust biomarker for the efficacy of osimertinib. Still, in a number of patients with NSCLC who harbour the EGFR T790M mutation, clinical efficacy remains very limited, which suggests primary resistance.

Jang et al. aimed to discover clinical predictive factors for the efficacy of osimertinib, and analysed patients with stage IV, EGFR T790M+ lung adenocarcinoma who were given osimertinib as salvage treatment in a retrospective study [1]. Various baseline clinical factors were investigated according to favourable or unfavourable osimertinib efficacy group. Unfavourable efficacy (primary resistance) was defined as progression-free survival (PFS) <6 months with osimertinib. A total of 30 patients were eligible for this analysis (19 in the favourable efficacy group and 11 in the unfavourable efficacy group). The favourable efficacy group consisted of more patients aged ≥60 years at the time of lung cancer diagnosis (P=0.058), with baseline neutrophil-to-lymphocyte ratio (NLR) ≤3.5 (P=0.058), and who had received pre-osimertinib treatment with first generation EGFR TKI (gefintinib or erlotinib) rather than second generation EGFR TKI (afatinib) (P=0.088).

It was found that PFS of favourable and unfavourable efficacy groups with osimertinib was 9.9 months (95% CI 9.5-10.3) and 3.3 months (95% CI 2.4-4.2), respectively (P<0.001). The response rate of osimertinib was 89.5% vs 18.2% (P<0.001). Age at the time of lung cancer diagnosis, Eastern Cooperative Oncology Group (ECOG) performance status, baseline NLR, pre-osimertinib EGFR TKI treatment, and PFS with previous EGFR TKI were revealed as potential predictive factors through Kaplan-Meier PFS estimation. Of these, regression analysis confirmed that only age at the time of lung cancer diagnosis ≥60 years (HR 0.292, 95% CI 0.104-0.819, P=0.019) and baseline NLR ≤3.5 (HR 0.238, 95% CI 0.083-0.677, P=0.007) were good predictive factors for the efficacy of osimertinib (see Table). These easily identifiable predictive factors have been studied in a very small patient number. If they remain valid in larger patient numbers remains to be seen.

Table. Cox proportional hazard regression analysis [1]

1.  Jang SH, et al. P2.14-03. WCLC 2019.

Posted on 8 November 20195 March 2021