Dataset Information

Furmonertinib for EGFR-mutant advanced non-small cell lung cancer: a glittering diamond in the rough of EGFR-TKI.

ABSTRACT: The third-generation EGFR-TKIs, such as osimertinib, aumolertinib, and furmonertinib, have been recommended as the preferred treatment for EGFR-mutant advanced non-small cell lung cancer (NSCLC). Among them, furmonertinib shows several advantages in terms of clinical efficacy. Firstly, compared to osimertinib and aumolertinib, furmonertinib was the first EGFR-TKI with median progression-free survival (mPFS) of over 20.0 m (20.8 m) for advanced NSCLC with classical EGFR-mutations. Furthermore, furmonertinib achieved a mPFS of 18.1 m in advanced NSCLC with unfavorable prognostic factors, such as the 21 L858R mutation and central nervous system (CNS) metastasis, which is unrivalled by osimertinib. Secondly, furmonertinib is the only FDA-approved EGFR-TKI for breakthrough therapy in newly-diagnosed advanced NSCLC with EGFR ex20ins mutation. Thirdly, the relatively longer mPFS of 20.8 m was observed in furmonertinib compared to osimertinib and aumolertinib (15.2 m and 15.3 m) in EGFR-mutant advanced NSCLC with CNS metastases. More importantly, the efficacy of furmonertinib increases within the dose range of 80-240 mg per day. Finally, furmonertinib can be an optional treatment for advanced NSCLC patients who develop resistance to osimertinib or aumolertinib. In conclusion, furmonertinib may be a glittering star in the field of EGFR-TKI, which requires further exploration and expansion.

SUBMITTER: Ding J

PROVIDER: S-EPMC10910349 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Furmonertinib for EGFR-mutant advanced non-small cell lung cancer: a glittering diamond in the rough of EGFR-TKI.

Ding Jianghua J Ding Xingjing X Zeng Jiao J Liu Xiaoqun X

Frontiers in pharmacology 20240219

The third-generation EGFR-TKIs, such as osimertinib, aumolertinib, and furmonertinib, have been recommended as the preferred treatment for EGFR-mutant advanced non-small cell lung cancer (NSCLC). Among them, furmonertinib shows several advantages in terms of clinical efficacy. Firstly, compared to osimertinib and aumolertinib, furmonertinib was the first EGFR-TKI with median progression-free survival (mPFS) of over 20.0 m (20.8 m) for advanced NSCLC with classical EGFR-mutations. Furthermore, fu ...[more]

PMID: 38440180

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Project description:Treatment options for epidermal growth factor receptor (EGFR)-mutant advanced non-small cell lung cancer (NSCLC) following tyrosine kinase inhibitor (TKI) failure are limited, and platinum-based chemotherapy remains the main treatment. The development of effective immunotherapy for this disease has been challenging. In the present study, 37 patients with EGFR-mutant advanced NSCLC who were treated with programmed cell death-1 (PD-1) inhibitor-based combinations after TKI failure were reviewed. The total cohort had a median progression-free survival (mPFS) of 5.2 months (95% CI, 4.077-6.323 months) and a median overall survival (mOS) of 18.3 months (95% CI, 12.932-23.668 months). Patients with Eastern Cooperative Oncology Group performance-status (ECOG-PS) scores of 0 or 1 had longer mPFS than those with ECOG-PS scores of 2 (5.4 vs. 2.4 months; P=0.006). In addition, a PFS benefit was observed in patients with EGFR T790M-negative compared with EGFR T790M-positive tumors (mPFS 6.2 vs. 4.4 months; P=0.041). Patients treated with immunotherapy-based combinations as a front-line therapy had a longer mPFS than those in which the combinations were used as a late-line therapy (6.2 vs. 2.4 months; P<0.001). PD-1 inhibitor combined with chemotherapy and bevacizumab did not show a clear advantage over PD-1 inhibitor combined with chemotherapy alone (mPFS, 6.2 vs. 4.4 months; P=0.681), although it resulted in an improved overall response rate (ORR) and disease control rate. Notably, the 7 patients with a programmed cell death ligand-1 (PD-L1) tumor proportion score of ≥50% had an ORR of 100% and an mPFS of 8.3 months. Therefore, it is suggested that PD-1 inhibitor-based combinations should be a priority treatment option in selective populations, such as those with low ECOG-PS scores, T790M-negative status or high PD-L1 expression in EGFR-mutant NSCLC after TKI failure. The use of immunotherapy and chemotherapy in combination with antiangiogenic agents appears to be a promising combination therapy for such patients.

Project description:BackgroundThe efficacy of neoadjuvant treatment with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) monotherapy in patients with stage III-N2 EGFR-mutant remains unsatisfactory. This study explored the potential benefits of combining first-generation EGFR-TKI with chemotherapy as a neoadjuvant treatment for patients with stage III-N2 EGFR-mutant non-small cell lung cancer (NSCLC).Patients and methodsThe medical records of patients with III-N2 EGFR-mutant NSCLC who received neoadjuvant therapy with EGFR-TKI at Shanghai Chest Hospital from October 2011 to October 2022 were retrospectively reviewed. Patients with stage III-N2 EGFR-mutant NSCLC who received first-generation TKI combined with chemotherapy as neoadjuvant treatment were included in the combination group, and those who received EGFR-TKI monotherapy were included in the monotherapy group. The study assessed the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, disease-free survival (DFS), overall survival (OS), downstaging rates of pathologic lymph nodes (from stage N2 to N1 or N0), major pathologic response (MPR) rate, pathological complete response (PCR) rate, and safety.ResultsA total of 74 631 patients with EGFR-mutant NSCLC were screened, and 60 patients were included, 7 of whom did not undergo surgery after neoadjuvant targeted therapy. Of the remaining 53 patients, 15 received first-generation EGFR-TKI combined with chemotherapy as neoadjuvant treatment, and 38 received EGFR-TKI monotherapy. The median follow-up time was 44.12 months. The ORR was 50.0% (9/18) in the combination group and 40.5% (17/42) in the monotherapy group (P = .495). The MPR rate was 20.0% (3/15) and 10.5% (4/38) in the combination and monotherapy groups, respectively (P = .359). No patients achieved PCR in the combination group, while 3 (7.89%) attained PCR in the monotherapy group. The 2 groups did not differ in N2 downstaging rate (P = .459). The median DFS was not reached in the combination group, while it was 23.6 months (95% CI: 8.16-39.02) in the monotherapy group (P = .832). Adverse events observed were consistent with those commonly associated with the 2 treatments.ConclusionCombination therapy with first-generation EGFR-TKI and chemotherapy could be considered a neoadjuvant treatment option for patients with stage III-N2 EGFR-mutant NSCLC, exhibiting acceptable toxicity. However, regarding short-term efficacy, combination therapy did not demonstrate superiority over EGFR-TKI monotherapy. Long-term follow-up is warranted for a more accurate assessment of the DFS and OS.

Project description:BackgroundDespite the potent efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in the treatment of EGFR-mutant non-small cell lung cancer (NSCLC) patients, drug resistance inevitably ensues, and there remains a paucity of treatment options in clinical practice.MethodsWe identified patients with EGFR-mutant advanced NSCLC presenting to Shanghai Pulmonary Hospital and Shanghai Chest Hospital between January 2015 and December 2020 treated with chemo-antiangiogenesis or chemo-immunotherapy combinations after EGFR-TKI resistance. Patient information was collected, and the objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) were assessed.ResultsA total of 144 patients who met our inclusion criteria were enrolled. Chemo-immunotherapy combinations achieved a higher objective response rate (ORR) compared with chemo-antiangiogenesis combinations (29.5% vs. 13.0%, P=0.018). The DCR was similar between the two groups (93.0% vs. 88.6%, P=0.585), as was the median PFS (7.59 vs. 6.90 months, P=0.552). In the subgroup analyses, patients who developed secondary T790M mutations after EGFR-TKI treatment were less likely to benefit from chemo-immunotherapy combinations than their T790M-negative counterparts (3.42 vs. 7.63 months, P=0.028). For patients who received chemo-antiangiogenesis combinations after TKI resistance, no significant difference was observed in the median PFS between T790M-positive and T790M-negative patients (median PFS: 5.33 vs. 7.46 months, P=0.202). Additionally, multivariate analysis showed that an elevated platelet count was independently associated with a worse PFS for both groups.ConclusionsThe efficacy of chemo-immunotherapy combinations was comparable to chemo-antiangiogenesis combinations after failure of EGFR-TKI therapy. For patients harboring EGFR T790M mutations, chemo-antiangiogenesis combinations may be the preferred therapeutic option. In addition, platelet count could be a potential prognostic factor for patients after failure of EGFR-TKI therapy. Further research should be conducted on larger populations and in a prospective setting.

Dataset Information

Furmonertinib for EGFR-mutant advanced non-small cell lung cancer: a glittering diamond in the rough of EGFR-TKI.

Publications

Furmonertinib for EGFR-mutant advanced non-small cell lung cancer: a glittering diamond in the rough of EGFR-TKI.

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