Efficacy and Safety of Afatinib for EGFR-mutant Non-small Cell Lung Cancer, Compared with Gefitinib or Erlotinib

Kim, Youjin; Lee, Se‐Hoon; Ahn, Jin Seok; Ahn, Myung‐Ju; Park, Keunchil; Sun, Jong‐Mu

doi:10.4143/crt.2018.117

Cited by 74 publications

(100 citation statements)

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“…Kim et al revealed that in a subgroup of patients with 19del mutations, the median PFS of afatinib was significantly superior to gefitinib or erlotinib (19.1 vs. 15.0 and 16.3 months, respectively; P = 0.01). However, there was no such significant difference in the L858R subgroup ( P = 0.46) …”

Section: Discussionmentioning

confidence: 87%

“…These outcomes may lead to a tendency in clinical practice to prescribe afatinib to patients with 19del mutations. Several real‐world studies have also demonstrated this tendency and reported longer median PFS in common EGFR mutation groups . Kim et al revealed that in a subgroup of patients with 19del mutations, the median PFS of afatinib was significantly superior to gefitinib or erlotinib (19.1 vs. 15.0 and 16.3 months, respectively; P = 0.01).…”

Section: Discussionmentioning

confidence: 89%

“…Several real-world studies have also demonstrated this tendency and reported longer median PFS in common EGFR mutation groups. [19][20][21] Kim et al revealed that in a subgroup of patients with 19del mutations, the median PFS of afatinib was significantly superior to gefitinib or erlotinib (19.1 vs. 15.0 and 16.3 months, respectively; P = 0.01). However, there was no such significant difference in the L858R subgroup (P = 0.46).…”

Section: Discussionmentioning

confidence: 99%

“…However, there was no such significant difference in the L858R subgroup (P = 0.46). 19 Combined analysis of the results of the LUX-Lung 2, 3, and 6 trials suggests that patients with point mutations or duplications in exons 18-21 could also achieve a median PFS of 10.7 months (95% CI 5.6-14.7). 12 However, in our study, the median PFS of uncommon EGFR mutant patients was only 5.2 months in the first-line setting.…”

Section: Discussionmentioning

confidence: 99%

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Efficacy and safety of afatinib in a Chinese population with advanced lung adenocarcinoma with sensitive EGFR mutations

et al. 2019

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Background Afatinib is an irreversible ErbB family blocker that improves progression‐free survival (PFS) of advanced EGFR ‐mutant lung adenocarcinoma compared to chemotherapy. However, afatinib leads to more adverse events than first‐generation EGFR inhibitors. Hence, exploration of the optimal afatinib initial dose and its efficacy and safety in Asian patients has drawn extensive attention. Methods We retrospectively evaluated demographic and clinical information, survival data, and adverse events in advanced non‐small cell lung cancer patients treated with afatinib from 27 February 2017 to 30 October 2018. Results A total of 60 patients were included in the study. Thirty‐nine (65%) patients received afatinib as first‐line treatment. The median PFS was 12.3 months (95% confidence internal 7.6–17.0). Multivariate Cox regression analysis revealed that age, gender, smoking history, baseline brain metastasis status, afatinib starting dose, and mutation type did not significantly influence PFS. No significant difference in median PFS between patients treated with an initial dose of afatinib of 40 mg or 30 mg, either in the first‐line (14.5 vs. 5.2 months; P = 0.101) or in a second or later‐line setting (3.0 vs. 5.0 months; P = 0.375) was observed. The incidence of all grades of rash/acne (92.5% vs. 61.1%; P = 0.011) and paronychia (82.5% vs. 50.0%; P = 0.010) in the 40 mg group was significantly higher than in the 30 mg group. Conclusion First‐line afatinib treatment is beneficial for advanced lung adenocarcinoma patients with sensitive EGFR mutations. Initial dose and baseline brain metastasis status do not significantly impact PFS.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Efficacy and safety of afatinib in a Chinese population with advanced lung adenocarcinoma with sensitive EGFR mutations

et al. 2019

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“…Erlotinib-treated patients of European origin with EGFR-positive adenocarcinoma showed increased PFS (9.7 vs. 5.2 months) compared to the chemotherapy-treated group in the EURTAC trial (14). In a face-to-face comparison of three TKIs (erlotinib, gefitinib and afatinib), afatinib showed the highest efficacy in terms of PFS duration (14 vs. 13.7 vs. 19.1 months, respectively) (15). Erlotinib is also used as a second-line or further treatment in patients with SCC due to more favorable toxicity profile compared to conventional chemotherapy (16).…”

Section: Discussionmentioning

confidence: 99%

Non-small Cell Lung Cancer as a Chronic Disease – A Prospective Study from the Czech TULUNG Registry

Bratová

Skřičková

Pešek

et al. 2019

In Vivo

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Aim: To compare survival outcomes in patients with non-small cell lung cancer (NSCLC) treated with modern-era drugs (antifolates, antiangiogenics, tyrosine kinase and anaplastic lymphoma kinase inhibitors, immunotherapy) with treatment initiation in 2011-12 and 2015-16, respectively. Patients and Methods: Prospective data from Czech TULUNG Registry (960 patients from 2011-12 and 512 patients from 2015-16) were analyzed. Kaplan-Meier analysis was used to estimate overall survival (OS) and progression-free survival (PFS); Cox proportional hazards model to assess factors associated with 2-year survival. Results: Survival at 2 years was more frequent in cohort 2015-16 compared to cohort 2011-12 (43.2% vs. 24% for adenocarcinoma; p<0.001 and 28.7% vs. 11.8% for squamous-cell lung carcinoma; p=0.002). Assignment to cohort 2015-16 and treatment multilinearity (two or more lines in sequence) were associated with higher probability of 2-year survival (hazard ratio=0.666 and hazard ratio=0.597; p<0.001). Comparison of 2-year survivors from both cohorts showed no differences. Conclusion: Survival at 2 years probability in stage IIIB-IV NSCLC doubled between 2011-12 and 2015-16; advanced-stage NSCLC may be considered a chronic disease in a large proportion of patients. With the exception of non-melanoma skin carcinoma, lung cancer is the leading form of cancer worldwide with alarming incidence and mortality. In 2018, as many as 2,093,876 new cases were reported worldwide (1) and Iung cancer claimed 1,761,007 lives (2). Incidence in Central and Eastern Europe in 2018 was 149,013 cases, while mortality was 131,369 (2). In the Czech Republic, 6,782 new cases of lung cancer were reported in 2016 (3). The most widely used anticancer agents in the treatment of non-small cell lung cancer (NSCLC) include various chemotherapeutic drugs as well as newer agents [antifolates, antiangiogenic drugs, tyrosine kinase inhibitors (TKIs), anaplastic lymphoma kinase (ALK) inhibitors and immunotherapy]. The newer drugs facilitate a more targeted and personalized treatment. Some of the newly synthesized agents reach even higher progression-free survival (PFS) 369 This article is freely accessible online.

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Novel bioactive 2‐phenyl‐4‐aminopyrimidine derivatives as EGFR^{Del19/T790M/C797S} inhibitors for the treatment of non‐small cell lung cancer

Xu,

Zhou,

et al. 2023

Archiv der Pharmazie

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Overexpression of the epidermal growth factor receptor (EGFR) has been implicated in the development of non‐small‐cell lung cancer (NSCLC). Thus, EGFR is an effective drug target for the treatment of NSCLC, and developing fourth‐generation EGFR inhibitors to overcome the resistance mediated by T790M/C797S mutations are currently under investigation. In this study, based on the binding model between Angew2017‐7634‐1 and EGFRT790M/C797S, several series of 2‐phenyl‐4‐aminopyrimidine derivatives were designed and synthesized. The bioactivity of these compounds was evaluated and it is suggested that compound A23 could effectively inhibit the proliferation of Ba/F3‐EGFRDel19/T790M/C797S and H1975‐EGFRL858R/T790M cells, with an IC50 of 0.22 ± 0.07 and 0.52 ± 0.03 μM, respectively. Meanwhile, the kinase activity of A23 against EGFRL858R/T790M and EGFRDel19/T790M/C797S was also evaluated, with an IC50 of 0.33 and 0.133 μM, respectively. Moreover, compound A23 was further evaluated in the H1975 xenograft models with significant in vivo tumor growth inhibitions of 25.5%, which means that A23 could effectively inhibit the growth of tumor cells and promote the death of tumor cells. As a result, A23 could be identified as a novel potential EGFRDel19/T790M/C797S inhibitor.

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Efficacy and Safety of Afatinib for EGFR-mutant Non-small Cell Lung Cancer, Compared with Gefitinib or Erlotinib

Abstract: First-line afatinib showed satisfactory efficacy data and manageable toxicity profiles.

Cited by 74 publications

References 20 publications

Efficacy and safety of afatinib in a Chinese population with advanced lung adenocarcinoma with sensitive EGFR mutations

Efficacy and safety of afatinib in a Chinese population with advanced lung adenocarcinoma with sensitive EGFR mutations

Non-small Cell Lung Cancer as a Chronic Disease – A Prospective Study from the Czech TULUNG Registry

Novel bioactive 2‐phenyl‐4‐aminopyrimidine derivatives as EGFR^{Del19/T790M/C797S} inhibitors for the treatment of non‐small cell lung cancer

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Efficacy and Safety of Afatinib for EGFR-mutant Non-small Cell Lung Cancer, Compared with Gefitinib or Erlotinib

Abstract: First-line afatinib showed satisfactory efficacy data and manageable toxicity profiles.

Cited by 74 publications

References 20 publications

Efficacy and safety of afatinib in a Chinese population with advanced lung adenocarcinoma with sensitive EGFR mutations

Efficacy and safety of afatinib in a Chinese population with advanced lung adenocarcinoma with sensitive EGFR mutations

Non-small Cell Lung Cancer as a Chronic Disease – A Prospective Study from the Czech TULUNG Registry

Novel bioactive 2‐phenyl‐4‐aminopyrimidine derivatives as EGFRDel19/T790M/C797S inhibitors for the treatment of non‐small cell lung cancer

Contact Info

Product

Resources

About

Novel bioactive 2‐phenyl‐4‐aminopyrimidine derivatives as EGFR^{Del19/T790M/C797S} inhibitors for the treatment of non‐small cell lung cancer