Real-World Data About Treatment Outcomes for Patients with EGFR-Mutated NSCLC Resistance to Osimertinib and Platinum-Based Chemotherapy

Adv Ther. 2023 Oct;40(10):4545-4560. doi: 10.1007/s12325-023-02616-9. Epub 2023 Aug 12.

Abstract

Introduction: Docetaxel is an established standard therapy after osimertinib and platinum-based doublet chemotherapy (Pt-doublet) for locally advanced or metastatic non-small cell lung cancer (NSCLC) with an epidermal growth factor receptor gene (EGFR) mutation. To facilitate future therapeutic developments in these patients after treatment with osimertinib and Pt-doublet, we estimated the outcomes of currently used post-treatment therapies.

Methods: Data of patients with NSCLC who received at least one medication after osimertinib and Pt-doublet between April 2008 and August 2021 were extracted from the Medical Data Vision claims database. The duration of treatment (DoT) (first treatment after osimertinib and Pt-doublet) and overall survival (OS) were estimated. The index date was the first day on which the medication was prescribed.

Results: In total, 731 patients (mean age 64 years) were screened. The most frequent post-treatments were docetaxel-based chemotherapy (30.2%), immune checkpoint inhibitor (ICI) alone or in combination (17.2%), first-/second-generation EGFR-tyrosine kinase inhibitors (16.7%), osimertinib (16.3%), and Pt-doublet (5.2%). The median DoT and OS (95% confidence interval) of all post-treatments were 3.5 (3.27, 3.77) and 10.3 (9.3, 12.1) months, respectively, reflecting the median DoT (3.8 months) and OS (10.0 months) of docetaxel-based chemotherapy. Among all post-treatment regimens, ICIs resulted numerically the shortest [2.77 (2.33, 3.00) months] and osimertinib the longest [4.40 (3.47, 5.67) months] median DoT. The median OS was shortest in patients post-treated with ICIs [7.07 (5.40, 9.90) months] and longest in patients rechallenged with Pt-doublet (12.27 months), followed by patients post-treated with osimertinib (11.70 months). In a subset analysis of patients who received first-line osimertinib and second-line Pt-doublet as well as Pt-doublet immediately after osimertinib, those post-treated with ICIs had the shortest median DoT.

Conclusion: Given the limited real-world efficacy on EGFR-mutant NSCLC resistant to osimertinib and platinum-based chemotherapy, the development of more highly potent post-treatment therapies is warranted.

Keywords: Advanced non-small cell lung cancer; Epidermal growth factor receptor; Epidermal growth factor receptor-tyrosine kinase inhibitor; Medical data vision; Osimertinib; Tyrosine kinase inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Docetaxel / therapeutic use
  • ErbB Receptors
  • Genes, erbB-1
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Middle Aged
  • Mutation
  • Platinum / adverse effects
  • Platinum / therapeutic use
  • Protein Kinase Inhibitors / therapeutic use
  • Treatment Outcome

Substances

  • osimertinib
  • Docetaxel
  • Platinum
  • ErbB Receptors
  • Protein Kinase Inhibitors
  • EGFR protein, human