Central Nervous System Efficacy of Furmonertinib (AST2818) Versus Gefitinib as First-Line Treatment for EGFR-Mutated NSCLC: Results From the FURLONG Study

Shi, Yuankai; Chen, Gongyan; Wang, Xiang; Liu, Yunpeng; Wu, Lin; Hao, Yanrong; Liu, Chunling; Zhu, Shuang; Zhang, Xiaodong; Li, Yuping; Liu, Jiwei; Cao, Lejie; Cheng, Ying; Zhao, Hui; Zhang, Shucai; Zang, Aimin; Cui, Jiuwei; Feng, Jian; Yang, Nong; Liu, Fei; Jiang, Yong; Gu, Chuan

doi:10.1016/j.jtho.2022.07.1143

Cited by 28 publications

(24 citation statements)

References 26 publications

(38 reference statements)

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“…Second, the efficacy of furmonertinib 240 mg orally once daily did not show a promising ORR possibly due to the small sample size, although the median CNS-PFS was NR with furmonertinib 240 mg orally once daily, and all the patients with 160 mg or 240 mg orally once daily furmonertinib achieved CNS disease control. Third, the definition of CNS-PFS in this pooled post-hos analysis was consistent with previous published CNS analysis of third-generation EGFR TKIs including AURA extension and AURA2 pooled [ 31 ], FLAURA [ 32 ], FURLONG [ 19 ], however, the observed treatment benefit in the CNS-PFS analysis might be influenced as patients did not continue to receive brain scans following disease progression (irrespective of site of progression) or discontinuation from study with no CNS progression or death were censored at date last evaluable CNS assessment.…”

Section: Discussionsupporting

confidence: 85%

“…In a phase 2b study, the CNS objective response rate (ORR) of furmonertinib 80 mg orally once daily in EGFR T790M mutated NSCLC patients was 66% and the median CNS-PFS was 11.6 months [ 17 ]. In the phase 3 FURLONG study, furmonertinib was associated with higher PFS and CNS-PFS compared with gefitinib in EGFR sensitizing mutation positive, untreated, CNS metastatic patients [ 18 , 19 ]. These data had demonstrated the CNS efficacy of furmonertinib 80 mg orally once daily, but the evidence of other doses for CNS metastases was lacking.…”

Section: Introductionmentioning

confidence: 99%

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Central nervous system efficacy of furmonertinib (AST2818) in patients with EGFR T790M mutated non-small cell lung cancer: a pooled analysis from two phase 2 studies

Zhang

et al. 2023

BMC Med

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Background 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. Methods 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. Results 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. Conclusions Furmonertinib showed promising CNS efficacy in doses of 80 mg orally once daily or higher in patients with EGFR T790M mutated NSCLC. Trial registration 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.

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Section: Discussionsupporting

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Central nervous system efficacy of furmonertinib (AST2818) in patients with EGFR T790M mutated non-small cell lung cancer: a pooled analysis from two phase 2 studies

Zhang

et al. 2023

BMC Med

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“…Not surprisingly furmonertinib achieved superior PFS over gefitinib regardless of CNS metastasis. 21 More granular analysis of the FURLONG trial focusing on the CNS PFS also demonstrated superior CNS PFS of furmonertinib over gefitinib with an HR of 0.40. Importantly, the CNS PFS advantage for furmonertinib was similar for del19 or L858R patients 21 and compares favorably to the HR for CNS PFS in the overall FLAURA 22 ( Figure 2B ).…”

Section: Introductionmentioning

confidence: 98%

“… 21 More granular analysis of the FURLONG trial focusing on the CNS PFS also demonstrated superior CNS PFS of furmonertinib over gefitinib with an HR of 0.40. Importantly, the CNS PFS advantage for furmonertinib was similar for del19 or L858R patients 21 and compares favorably to the HR for CNS PFS in the overall FLAURA 22 ( Figure 2B ). The numerical value of CNS PFS in the furmonertinib arm of FURLONG was similar to the osimertinib arm of FLAURA but given the CNS PFS are constrained by the difference in patient characteristics (sex, age, number of CNS lesions, EGFR mutation subtype: del19 versus L858R, smoking status), we are comparing HRs rather than the actual CNS PFS.…”

Section: Introductionmentioning

confidence: 98%

Spotlight on Furmonertinib (Alflutinib, AST2818). The Swiss Army Knife (del19, L858R, T790M, Exon 20 Insertions, “uncommon-G719X, S768I, L861Q”) Among the Third-Generation EGFR TKIs?

Zhang¹,

Ou²

2022

LCTT

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Osimertinib, a third-generation (3G) epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is now considered the standard of care for the first-line (1L) treatment of advanced EGFR + NSCLC due to statistically significant improved progression-free survival (PFS) and overall survival (OS) compared with first-generation (1G) treatment from the FLAURA trial. Recently two other 3G EGFR TKIs (aumolertinib and furmonertinib) have been approved in China for treatment of EGFR T790M+ NSCLC. Randomized Phase 3 trials of these two 3G EGFR TKIs have also demonstrated PFS over gefitinib respectively. Among these two Chinese home-grown, 3G EGFR TKIs, furmonertinib seems to most closely resemble osimertinib in terms of dosing regimen, efficacy and adverse events profile. In this article, we reviewed the clinical activity and adverse events of furmonertinib at 80 mg daily (approved dose), potential usage of 160 mg daily for CNS metastasis in EGFR + NSCLC, and usage of 160 mg or 240 mg daily in EGFR exon20 insertion positive ( EGFRex20ins +) NSCLC patients.

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“…In the AENEAS study, almonertinib achieved longer median CNS-PFS over gefitinib in cFAS [29.0 vs 8.3 months; HR: 0.323 (95% CI: 0.181–0.576); p < 0.0001] [ 29 ]. Furmonertinib achieved a median CNS-PFS of 11.6 (95% CI: 8.3–13.8) months for EGFR T790M mutated patients in its phase IIb study for the cFAS and further prolonged the median CNS-PFS while compared with gefitinib in cFAS (20.8 vs 9.8 months; HR: 0.40 [95% CI: 0.23–0.71]; p = 0.0011) in the FURLONG study [ 15 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Results of the phase IIa study to evaluate the efficacy and safety of rezivertinib (BPI-7711) for the first-line treatment of locally advanced or metastatic/recurrent NSCLC patients with EGFR mutation from a phase I/IIa study

Shi

Zhou

Zhao

et al. 2023

BMC Med

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Background Rezivertinib (BPI-7711) is a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). This phase IIa study was part of a phase I/IIa study (NCT03386955), aimed to evaluate the efficacy and safety of rezivertinib as the first-line treatment for patients with locally advanced or metastatic/recurrent EGFR mutated non-small cell lung cancer (NSCLC). Methods Patients received the first-line treatment of 180 mg rezivertinib orally once daily until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was the objective response rate (ORR) assessed by blinded independent central review (BICR). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. Results From Jun 12, 2019, to Oct 17, 2019, 43 patients were enrolled. At the data cutoff date on Dec 23, 2021, the ORR by BICR was 83.7% (95% CI: 69.3–93.2%). The median DoR was 19.3 (95% CI: 15.8–25.0) months. The median PFS by BICR was 20.7 (95% CI: 13.8–24.8) months and 22.0 (95% CI: 16.8–26.3) months by investigators. Data on OS was immature. Totally, 40 (93.0%) patients had at least one treatment-related adverse event while 4 (9.3%) of them were grade ≥ 3. Conclusions Rezivertinib (BPI-7711) showed promising efficacy and a favorable safety profile for the treatment among the locally advanced or metastatic/recurrent NSCLC patients with EGFR mutation in the first-line setting. Trial registration ClinicalTrials.gov, NCT03386955.

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Central Nervous System Efficacy of Furmonertinib (AST2818) Versus Gefitinib as First-Line Treatment for EGFR-Mutated NSCLC: Results From the FURLONG Study

Cited by 28 publications

References 26 publications

Central nervous system efficacy of furmonertinib (AST2818) in patients with EGFR T790M mutated non-small cell lung cancer: a pooled analysis from two phase 2 studies

Central nervous system efficacy of furmonertinib (AST2818) in patients with EGFR T790M mutated non-small cell lung cancer: a pooled analysis from two phase 2 studies

Spotlight on Furmonertinib (Alflutinib, AST2818). The Swiss Army Knife (del19, L858R, T790M, Exon 20 Insertions, “uncommon-G719X, S768I, L861Q”) Among the Third-Generation EGFR TKIs?

Results of the phase IIa study to evaluate the efficacy and safety of rezivertinib (BPI-7711) for the first-line treatment of locally advanced or metastatic/recurrent NSCLC patients with EGFR mutation from a phase I/IIa study

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