P3.01-93 Osimertinib-Related Hematological and Pulmonary Toxicities in Advanced NSCLC Patients: Combined Analysis of Phase III Trials

Abstract

In both epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) sensitizing and EGFR T790M resistance mutations in patients with advanced non-small-cell lung cancer (NSCLC), osimertinib, a third-generation and irreversible oral EGFR-TKI, has been shown to improve survival in studies. We performed a systematic review and meta-analysis of phase III randomized controlled trials (RCT) to determine the risk of hematological and pulmonary toxicities among patients with advanced NSCLC treated with osimertinib. We undertook a comprehensive literature search using MEDLINE, EMBASE databases and meeting abstracts from inception through March 2018. Phase III RCTs that mention hematological and pulmonary toxicities as adverse effects were incorporated in the analysis. The primary meta- analytic approach was a fixed effects model using the Mantel-Haenszel (MH) method. It was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). A total of 971 patients with advanced NSCLC from two phase III studies were eligible for analysis. The study arm used osimertinib while the control arm utilized either chemotherapy (carboplatin/cisplatin+ pemetrexed) or standard EGFR-TKIs (gefitinib or erlotinib). The randomization ratio was 1:1 in the FLAURA study and 2:1 in the AURA3 study. Osimertinib was utilized in T790M-positive advanced NSCLC after prior first-line EGFR-TKIs in the AURA3 study (n= 556) and as first-line treatment in the FLAURA study (n= 415). The RR of all-grade side effects were as follows: anemia, 0.594 (95% CI: 0.433 – 0.814, p = 0.001); cough, 1.122 (95% CI: 0.829 – 1.520, p = 0.455); dyspnea, 1.143 (95% CI: 0.784 – 1.666; p = 0.487); and ILD, 2.378 (95% CI: 0.984 – 5.744; p = 0.054). The RR of high-grade adverse effects were as follows: anemia, 0.175 (95% CI: 0.072 – 0.425, p < 0.001); neutropenia, 0.293 (95% CI: 0.138 – 0.623; p = 0.001); thrombocytopenia, 0.183 (95% CI: 0.060 – 0.564, p = 0.003); pneumonia, 1.237 (95% CI: 0.442 – 3.459; p = 0.685); dyspnea, 0.895 (95% CI: 1.192 – 4.175; p = 0.888); and ILD, 1.238 (95% CI: 0.404 – 3.789; p = 0.708). Our meta-analysis demonstrated that patients on osimertinib experienced a significant decrease in the risk of hematological toxicities, compared to control arm. Moreover, no increase in the risk of pulmonary toxicities was noted in the osimertinib group.