UNASSIGNED: Furmonertinib showed superior efficacy compared with gefitinib as first-line therapy in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) in the FURLONG study. Here we present prespecified secondary endpoints of patient-reported outcomes (PRO).
UNASSIGNED: In this multicentre, double-blind, double-dummy, randomised phase 3 study, patients were 1:1 randomly assigned to receive furmonertinib 80 mg once daily or gefitinib 250 mg once daily. PROs assessed by the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 and Quality-of-Life Questionnaire Lung Cancer 13 were analysed using a mixed model for repeated measures and time-to-event analyses. A difference in score of 10 points or more was deemed clinically relevant.
UNASSIGNED: Three hundred and fifty-seven patients (furmonertinib group, n = 178; gefitinib group, n = 179) received at least one dose of the study drug, all of whom completed at least one PRO assessment. Statistically significant difference of overall score changes from baseline favoured furmonertinib in physical functioning (between-group difference 2.14 [95% CI 0.25-4.04], p = 0.027), nausea/vomiting (-1.56 [95% CI -2.62 to -0.49], p = 0.004), appetite loss (-2.24 [95% CI -4.26 to -0.23], p = 0.029), diarrhoea (-3.36 [95% CI -5.19 to -1.54], p < 0.001), alopecia (-2.62 [95% CI -4.54 to -0.71], p = 0.007), and pain in other parts (-4.55 [95% CI -7.37 to -1.74], p = 0.002), but not reached clinical relevance. Time to deterioration in physical functioning (hazard ratio 0.63 [95% CI 0.42-0.94], p = 0.021), cognitive functioning (0.73 [95% CI 0.54-0.98], p = 0.034), nausea/vomiting (0.64 [95% CI 0.41-0.99], p = 0.042), appetite loss (0.63 [95% CI 0.43-0.92], p = 0.016), diarrhoea (0.63 [95% CI 0.46-0.85], p = 0.002), dyspnoea (0.72 [95% CI 0.53-0.98], p = 0.034), cough (0.67 [95% CI 0.44-1.00], p = 0.049), dysphagia (0.54 [95% CI 0.35-0.83], p = 0.004), and alopecia (0.62 [95% CI 0.42-0.90], p = 0.012) was longer with furmonertinib versus gefitinib.
UNASSIGNED: In patients with locally advanced or metastatic EGFR mutation-positive NSCLC, furmonertinib showed improved scores and delayed deterioration in several functioning and symptoms compared to gefitinib.
UNASSIGNED: Shanghai Allist Pharmaceutical Technology Co., Ltd and the National Science and Technology Major Project for Key New Drug Development (2017ZX09304015).

Furmonertinib (AST2818) is a brain penetrant pan-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) targeting both EGFR sensitizing mutations and T790M mutation. We report the pooled central nervous system (CNS) efficacy data of furmonertinib in patients with EGFR T790M mutated non-small cell lung cancer (NSCLC) from two phase 2 studies.
This was a pooled, post-hoc analysis of two phase 2 studies (NCT03127449 [phase 2a study of furmonertinib], NCT03452592 [phase 2b study of furmonertinib]). In the phase 2a study, patients received furmonertinib 40 mg, 80 mg, 160 mg, or 240 mg orally once daily. In the phase 2b study, all patients received furmonertinib 80 mg orally once daily. CNS efficacy of furmonertinib was analyzed in patients with baseline CNS lesions by an independent review center per Response Evaluation Criteria in Solid Tumors version 1.1.
A total of 132 patients with baseline CNS metastases were included in this analysis. In 52 patients with measurable CNS lesions, CNS objective response rates were zero (0/1), 65% (22/34), 85% (11/13), and 25% (1/4), and CNS disease control rates were zero (0/1), 97% (33/34), 100% (13/13), and 100% (4/4) in the 40 mg, 80 mg, 160 mg, and 240 mg orally once daily group, respectively. In patients with measurable or non-measurable CNS lesions, median CNS progression-free survival was 2.8 months (95% confidence interval [CI] 1.4-8.3), 11.6 months (95% CI 8.3-13.8), 19.3 months (95% CI 5.5-not available [NA]), and not reached (95% CI 2.8 months-NA) in the 40 mg, 80 mg, 160 mg, and 240 mg orally once daily group, respectively.
Furmonertinib showed promising CNS efficacy in doses of 80 mg orally once daily or higher in patients with EGFR T790M mutated NSCLC.
Both studies were registered on ClinicalTrial.gov. The phase 2a study was registered with NCT03127449 on April 25, 2017; The phase 2b study was registered with NCT03452592 on March 2, 2018.

Furmonertinib (AST2818) is a pan-EGFR tyrosine kinase inhibitor with central nervous system (CNS) antitumor activity. We report the CNS efficacy of furmonertinib compared with gefitinib in untreated EGFR-sensitizing mutation-positive NSCLC from the FURLONG study.
FURLONG was a randomized, double-blind, phase 3 study conducted in 55 hospitals in the People\'s Republic of China. Patients 1:1 randomly received furmonertinib 80 mg once daily or gefitinib 250 mg once daily treatment. At screening, all the patients underwent brain imaging examination. Patients with asymptomatic steady CNS metastases at baseline constituted this preplanned CNS subgroup analysis.
A total of 358 patients were enrolled in the FURLONG study. In the 133 (37%) patients who had measurable or nonmeasurable CNS lesions, CNS progression-free survival was 20.8 months (95% confidence interval [CI]: 15.2-25.3) in the furmonertinib group and 9.8 months (95% CI: 7.2-18.0) in the gefitinib group (hazard ratio = 0.40 [95% CI: 0.23-0.71], p = 0.0011). In the 60 patients (17%) who had measurable CNS lesions, CNS objective response rate was 91% (95% CI: 72-99) with furmonertinib and 65% (95% CI: 48-80) with gefitinib (OR = 6.82 [95% CI: 1.23-37.67], p = 0.0277). The least-square mean of CNS depth of response was 62% (95% CI: 51-72) in the furmonertinib group and 39% (95% CI: 30-47) in the gefitinib group, the mean difference was 23% (95% CI: 10-37, p = 0.0011).
Furmonertinib first-line treatment was found to have superior efficacy in CNS progression-free survival, CNS objective response rate, and CNS depth of response compared with gefitinib in patients with EGFR-mutated NSCLC with CNS metastases.

Alflutinib, or known as AST2818, is an irreversible tyrosine kinase inhibitor that selectively inhibits EGFR mutations, especially T790M. At present, alflutinib has undergone phase II/III clinical trials for non-small cell lung cancer (NSCLC) treatment in China. The present study aimed to analye the pharmacokinetics of alflutinib and its active metabolite AST5902 in a plasma sample of NSCLC patient. A sensitive and highly selective method was optimized and validated for the detection of alflutinib and AST5902 using a liquid chromatography-tandem mass spectrometry. After precipitating proteins with acetonitrile, alflutinib, AST5902 and AST2818-d3 (internal standard) were analyzed with a Waters BEH C18 column. The mobile phase was optimized with acetonitrile: ammonium acetate (2 mmol/L) containing 0.2% formic acid using gradient elution. Separation was achieved within a total chromatographic running time of 2.1 min. Quantification was carried out using positive ion multiple reaction monitoring mode at ion transitions m/z 569.3→441.2, 555.1→498.2 and 572.3→441.2 for alflutinib, AST5902 and AST2818-d3, respectively. An excellent linearity was observed for alflutinib and AST5902 within concentration ranges of 0.20-100 and 0.050-25.0 ng·mL-1, respectively. Notably, the lower limit of quantification for alflutinib and AST5902 were 0.20 and 0.050 ng/mL, respectively. The intra- and inter-day accuracy of alflutinib were 0.7-2.9%, while its intra- and inter-assay precision were ≤9.1% and ≤10.5%, respectively. The accuracy of AST5902 was within -0.2-3.9%, while the intra- and inter-assay precision were ≤8.0% and ≤8.6%, respectively. The recoveries of the analysts remained constant and could be reproduced at different concentrations. Furthermore, this analytical method could be applied to determine the pharmacokinetic analysis of alflutinib and AST5902 in human plasma.