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. 2021 Nov 29:13:17588359211059874.
doi: 10.1177/17588359211059874. eCollection 2021.

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  1 , Maximilian Hochmair  2 , Urska Janzic  3 , Elizabeth Dudnik  4 , Andriani Charpidou  5 , Adam Płużański  6 , Tudor Ciuleanu  7 , Ivan Shterev Donev  8 , Judith Elbaz  9 , Jørgen Aarøe  10 , René Ott  11 , Nir Peled  12
Affiliations

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 et al. Ther Adv Med Oncol. .

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.

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Conflict of interest statement

Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AA received honoraria from AstraZeneca, BMS, Eli Lilly, MSD, Pfizer, Roche and Takeda outside the submitted work. MH received honoraria for speaker’s bureau from AstraZeneca, BMS, Boehringer Ingelheim, MSD, Roche and Takeda, and served on advisory boards for AstraZeneca, BMS, Boehringer Ingelheim, MSD, Roche and Takeda. UJ served on advisory councils or committees for AstraZeneca, Boehringer Ingelheim, MSD and Roche, and received honoraria from AstraZeneca, BMS, Boehringer Ingelheim, MSD, Pfizer and Roche. ED served on advisory councils or committees for AstraZeneca, BMS, Novartis, Pfizer, Roche, Sanofi, and Takeda, received honoraria from AstraZeneca, BMS, MSD, Novartis, Pfizer, Roche, Sanofi, Pfizer, and Takeda and received consulting fees from AstraZeneca, BMS, Novartis, Pfizer, Roche, Sanofi, and Takeda, all outside the submitted work. AC served on advisory councils or committees for ASTRA, Boehringer Ingelheim and MSD, received honoraria from ASTRA, BMS, MSD and Roche and received consulting fees from ASTRA and Boehringer Ingelheim, outside the submitted work. AP has received personal fees and non-financial support from AstraZeneca, BMS, Boehringer Ingelheim, Pfizer and Roche, and personal fees from MSD, and Takeda outside the submitted work. TC served on advisory councils or committees for Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim Janssen, MSD. Roche, and Pfizer outside the submitted work. ISD has no disclosures to declare. JE and JA are employees of AstraZeneca. RO is an employee of AstraZeneca AG and owns stocks/shares in AstraZeneca AG. NP served on advisory councils or committees for AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Eli Lilly, FoundationMedicine, Guardant360, Merck, MSD, Novartis, NovellusDx, Pfizer, Roche and Takeda, received honoraria and consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Eli Lilly, FoundationMedicine, Guardant360, Merck, MSD, Novartis, NovellusDx, Pfizer, Roche and Takeda, and received grants or funds from AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Eli Lilly, Merck, MSD, Novartis, Pfizer, Roche and Takeda.

Figures

Figure 1.
Figure 1.
Kaplan–Meier curves: (a) real-world progression-free survival on first-line EGFR-TKI treatment, (b) real-world progression-free survival on first-line EGFR-TKI treatment by country, (c) time to treatment discontinuation of first-line EGFR-TKI treatment, and (d) overall survival from initiation of first-line EGFR-TKI (per-protocol population). Censored patients are indicated with a cross. 95% equal precision band indicated with colored shading. 1 L, first-line; CI, confidence interval; EGFR-TKI, epidermal growth factor receptor tyrosine kinase inhibitor; NSCLC, non-small-cell lung cancer; OS, overall survival; rwPFS, real-world progression-free survival; TTD, time to treatment discontinuation.
Figure 2.
Figure 2.
Testing for EGFR T790M mutations after first-line progression (per-protocol population). 1 L, first-line; EGFR, epidermal growth factor receptor.
Figure 3.
Figure 3.
Osimertinib treatment in patients with first-line progression on EGFR-TKIs (n = 723) by EGFR T790M testing status. 5 L osimertinib treatment is in a patient with a T790M-positive test. 1 L, first-line; EGFR-TKI, epidermal growth factor receptor tyrosine kinase inhibitor.
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