P76.09 A Comparison of Sequential EGFR-TKI Therapy Versus First-Line Osimertinib in NSCLC: A Multi-Center, Retrospective Study

Abstract

Lung cancer remains the deadliest form of cancer. Several driver mutations have been identified of which targeted tyrosine kinase inhibitors (TKIs) have shown favorable response. Epidermal growth factor receptor (EGFR) is the most common driver mutation and is present in approximately 15% of adenocarcinomas. There are currently several TKIs approved for the use of EGFR mutated lung cancer. The FLAURA trial showed a progression free survival (PFS) and overall survival (OS) benefit with osimertinib compared to first generation EGFR TKIs. There is a paucity of data to support using a first or second generation EGFR TKI after progression on osimertinib. In this study, we aim to assess the outcomes of EGFR mutated lung cancer patients being treated with a first or second generation EGFR TKI compared to osimertinib. An IRB approved, multi-center, retrospective review of lung cancer patients receiving EGFR TKIs between 2014 and 2019 was conducted. Patients were included in this review if they had received an EGFR TKI for metastatic lung cancer in the front line setting. Patients were excluded if they had an active concomitant cancer, de novo T790M mutation, no EGFR mutations, or who were treated with chemotherapy as first line therapy. EGFR TKI was dichotomized as osimertinib vs all other EGFR TKIs. PFS and OS was estimated using the Kaplan-Meier product-limit method and first line EGFR TKI was compared using the log-rank test. A Cox proportional hazards model was used to examine the association between PFS and OS and EGFR TKI and various patient factors. A total of 172 were included in the analysis, 52 (30.2%) received osimertinib and 120 (69.8%) received another EGFR TKI (afatinib=25, gefitinib=1, erlotinib=94) as first line treatment. All but three of these patients (98%) were never or former smokers and 35% of patients had baseline brain metastasis. Sixty percent of patients had an exon 19 deletion, 33% exon 21 mutation and 7% had another EGFR mutation. The PFS rates at 12 and 18 months were 79.5% and 69.8% in the osimertinib group and 64.2% and 39.3% in the other EGFR TKI groups, respectively (p<0.0036). The adjusted Hazard Ratio (HR) for PFS (reference: osimertinib) was 2.59 (95% CI: 1.31 to 5.11) p<0.0064. Estimated OS at 12 and 18 months were 94.2% and 80.2% in the osimertinib group and 93.9% and 84.1% in the other EGFR TKI groups, respectively (p<0.6382). The adjusted HR for OS was 0.95 (95% CI, 0.37 to 2.44) p<0.9128. In this single institution retrospective review, osimertinib demonstrated a greater PFS compared to other EGFR TKIs at 12 and 18 months. Estimated OS were no different between the two groups. Additional follow up is needed to solidify the real world OS benefit of osimertinib to other EGFR TKIs.