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 Płużański; Tudor Ciuleanu; Ivan Shterev Donev; Judith Elbaz; Jørgen Aarøe; René Ott; Nir Peled

doi:10.1177/17588359211059874

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

Ther Adv Med Oncol. 2021 Nov 29:13:17588359211059874. doi: 10.1177/17588359211059874. eCollection 2021.

Authors

Affiliations

¹ Medical Oncology, Geneva University Hospital, Geneva, Switzerland.
² Department of Respiratory and Critical Care Medicine, Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Klinik Floridsdorf, Brünner Strasse 68, A-1210 Vienna, Austria.
³ Medical Oncology Department, University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia.
⁴ Davidoff Cancer Center Rabin Medical Center, Clalit Health Services, Petah Tikva, Israel.
⁵ Oncology Unit, 3rd Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece.
⁶ Department of Lung Cancer and Chest Tumors, The Maria Sklodowska Curie National Research Institute of Oncology, Warsaw, Poland.
⁷ Medical Oncology Department, Prof. Dr. Ion Chiricuta Oncology Institute and Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania.
⁸ Department of Medical Oncology, MHAT Nadezhda, Sofia, Bulgaria.
⁹ Oncology, AstraZeneca Israel, Hod Hasharon, Israel.
¹⁰ Oncology, AstraZeneca Nordic, Oslo, Norway.
¹¹ OBU Europe, AstraZeneca AG, Zug, Switzerland.
¹² Soroka Cancer Center, Beer-Sheva, Israel.

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.

Keywords: EGFR T790M testing; EGFR-TKI; NSCLC; attrition; real-world evidence.