Real-World Study of Osimertinib in Korean Patients with Epidermal Growth Factor Receptor T790M Mutation–Positive Non–Small Cell Lung Cancer

Abstract

Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment.Herein, we report on the use of osimertinib in patients with EGFR T790M mutation-positive non-small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea. Materials and MethodsPatients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints. ResultsA total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval (CI), 13.0-16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1-15.9). The median overall survival was 36.7 months (95% CI, 30.9-not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten (1.8%) patients, including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects. ConclusionOsimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation-positive in Korean patients with no new safety signals.

Real-world evidence of osimertinib in Chinese patients with EGFR T790M-positive non-small cell lung cancer: a subgroup analysis from ASTRIS study

“…On similar lines, a good response rate of 58.2% (95% CI 52.7–63.6) was achieved in the CNS metastases subgroup in our study which was in line with the AURA extension (Yang et al 2017 ) (64%, 95% CI 43–82), pooled analysis of AURA2/AURA extension (Ahn et al 2019 ) (59%, 95% CI 51–67) and ASTRIS Korean subgroup study (Cho et al 2020 ) (68%, 95% CI 61–74.5). The median TTD in patients with and without CNS metastases was found to be 12.6 months (95% CI: 11.2–13.9) and 15.2 months (95% CI 13.7–16.1), respectively in the present study which was consistent with ASTRIS Korean subgroup study (Cho et al 2020 ) (with CNS metastases: 11.2 months, 95% CI 9.4–14.8; without CNS metastases: 14.7 months, 95% CI 12.2–not reached) and Korean real-world study (Lee et al 2023 ) (with CNS metastases: 12.5 months, 95% CI 11.0–14.0; without CNS metastases: 15.9 months, 95% CI 14.8–17.0).…”

“…For initial EGFR T790M testing, however, liquid biopsy is recommended by the National Comprehensive Cancer Network guidelines as an alternative to tissue biopsy (John et al 2017 ). The median PFS observed in patients with T790M-positive status by plasma testing in the ASTRIS global study (9.7 months; 95% CI 8.6–10.3), AURA3 study (8.2 months; 95% CI: 6.8–9.7), Korean real-world study (11.0 months; 95% CI 9.0–12.6) was also comparable to our study (10.0 months; 95% CI 9.5–11.0) (Marinis et al 2019 ; Mok et al 2017 ; Lee et al 2023 ). A shorter PFS was observed in plasma EGFR T790M-positive patients in the ASTRIS Korean subgroup study (Cho et al 2020 ) (6.9 months; 95% CI 2.5–10.9).…”

“…The median PFS observed in our study was 11.7 months (95% CI 11.1–12.5), which was comparable with that reported in ASTRIS global population (Marinis et al 2019 ) (11.1 months; 95% CI 11.0–12.0) and in the previous osimertinib studies, notably AURA3 (Mok et al 2017 ) (10.1 months; 95% CI 8.3–12.3), AURA extension (Yang et al 2017 ) (12.3 months; 95% CI 9.5–13.8), AURA2(Goss et al 2016 ) (9.9 months; 95% CI 8.5–12.3), retrospective study by Peng et al (Peng et al 2021 ) (12.0 months; 95% CI 10.5–13.5), ASTRIS Korean subgroup (Cho et al 2020 ) (12.4 months; 95% CI 11.1–13.6), AURA3 Japanese subgroup (Akamatsu et al 2018 ) (12.5 months; 95% CI 6.9 to not calculated), and in a Phase III open-label study (Nie et al 2018 ) (10.2 months; 95% CI 8.27–9.75) but a recently published Korean real-world study reported a longer PFS (Lee et al 2023 ) (14.2 months; 95% CI 13.0–16.4) Several methods are available to detect the presence of EGFR T790M from tumor tissue or circulating tumor DNA from plasma (Spence et al 2021 ). Tumor tissue is generally preferred and is the current gold standard for detecting resistance mutations (John et al 2017 ).…”

“…The benefit of osimertinib treatment was also found to be extended to the subgroup of Chinese EGFR T790M mutation positive NSCLC patients with brain/leptomeningeal metastases reporting a median PFS of 11.0 months (95% CI 9.7–12.4). The findings were consistent with previous reports – AURA extension (Yang et al 2017 ) (7.1 months, 95% CI 4.2–12.3), pooled analysis of AURA2/AURA extension (Ahn et al 2019 ) (8.2 months, 95% CI 6.9–9.7 months) and AURA3 study (Mok et al 2017 ) (8.5 months, 95% CI 6.8–12.3), ASTRIS Korean subgroup study (Cho et al 2020 ) (median PFS: 10.8 months; 95% CI 9.5–11.5) and Korean real-world study (Lee et al 2023 ) (12.1 months, 95% CI 10.3–14.7). On similar lines, a good response rate of 58.2% (95% CI 52.7–63.6) was achieved in the CNS metastases subgroup in our study which was in line with the AURA extension (Yang et al 2017 ) (64%, 95% CI 43–82), pooled analysis of AURA2/AURA extension (Ahn et al 2019 ) (59%, 95% CI 51–67) and ASTRIS Korean subgroup study (Cho et al 2020 ) (68%, 95% CI 61–74.5).…”

Real-world clinical evidence of lazertinib use in acquired EGFR T790M mutated non-small cell lung cancer

“…In addition, the objective response rate of our study population was 72.8%, also numerically higher than that (55.3%) observed in the same previous trial ( 7 ). Although careful interpretation is warranted given the indirect comparison, these data also showed numerically better outcomes compared to real-world evidence observed in an EGFR T790M-mutated Korean population treated with another third-generation EGFR-TKI (osimertinib), which exhibited a 12-month PFS rate of 56.5% ( 9 ).…”