Treatment patterns, testing practices, and outcomes in the pre-FLAURA era for patients with EGFR mutation-positive advanced NSCLC: a retrospective chart review (REFLECT)

Alfredo Addeo, Maximilian Hochmair, Urska Janzic, Elizabeth Dudnik, Andriani Charpidou, Adam Płużanński, Tudor Ciuleanu, Ivan Shterev Donev, Judith Elbaz, Jørgen Aarøe, René Ott, Nir Peled

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: For epidermal growth factor receptor mutation-positive (EGFRm) non-small-cell lung cancer (NSCLC), EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are the preferred first-line (1 L) treatment in the advanced setting. Osimertinib, a third-generation EGFR-TKI, received full approval in 2017 for second-line (2 L) treatment of EGFR T790M-positive NSCLC. The REFLECT study characterizes real-world treatment/testing patterns, attrition rates, and outcomes in patients with EGFRm advanced NSCLC treated with 1 L first-/second-generation (1G/2G) EGFR-TKIs before 1 L osimertinib approval. Methods: Retrospective chart review (NCT04031898) of European/Israeli adults with EGFRm unresectable locally advanced/metastatic NSCLC, initiating 1 L 1G/2G EGFR-TKIs 01/01/15–30/06/18 (index date). Results: In 896 patients (median follow-up of 21.5 months), the most frequently initiated 1 L EGFR-TKI was afatinib (45%). Disease progression was reported in 81%, including 10% (86/896) who died at 1 L. By the end of study, most patients discontinued 1 L (85%), of whom 33% did not receive 2 L therapy. From index, median 1 L real-world progression-free survival was 13.0 (95% confidence interval (CI): 12.3–14.1) months; median overall survival (OS) was 26.2 (95% CI: 23.6–28.4) months. 71% of patients with 1 L progression were tested for T790M; 58% were positive. Of those with T790M, 95% received osimertinib in 2 L or later. Central nervous system (CNS) metastases were recorded in 22% at index, and 15% developed CNS metastases during treatment (median time from index 13.5 months). Median OS was 19.4 months (95% CI: 17.1–22.1) in patients with CNS metastases at index, 24.8 months (95% CIs not available) with CNS metastases diagnosed during treatment, and 30.3 months (95% CI: 27.1, 33.8) with no CNS metastases recorded. Conclusion: REFLECT is a large real-world study describing treatment patterns prior to 1 L osimertinib availability for EGFRm advanced NSCLC. Given the attrition rates highlighted in the study and the impact of CNS progression on outcomes, offering a 1 L EGFR-TKI with CNS penetration may improve patient outcomes in this treatment setting.

Original languageEnglish
JournalTherapeutic Advances in Medical Oncology
Volume13
DOIs
StatePublished - Nov 2021
Externally publishedYes

Keywords

  • attrition
  • EGFR T790M testing
  • EGFR-TKI
  • NSCLC
  • real-world evidence

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