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Journal of Oncology 2023The aim of this study is to evaluate the efficacy and safety of afatinib in the treatment of non-small cell lung cancer (NSCLC) patients with brain metastasis based on...
AIM
The aim of this study is to evaluate the efficacy and safety of afatinib in the treatment of non-small cell lung cancer (NSCLC) patients with brain metastasis based on meta-analysis.
METHODS
Related literatures were searched in the following databases: EMbase, PubMed, China Knowledge Network (CNKI), Wanfang, Weipu, Google Scholar, the China Biomedical Literature Service System, and other databases. Clinical trials and observational studies that met the requirements were selected for meta-analysis using Revman 5.3. The hazard ratio (HR) was used as an indicator of the impact of afatinib.
RESULTS
A total of 142 related literatures were acquired, but after screening, five literatures were selected for data extraction. The following indices were compared: the progression-free survival (PFS), overall survival (OS), and common adverse reactions (ARs) of grade 3 and above. A total of 448 patients with brain metastases were included and were divided into two groups: the control group (no afatinib treatment, with chemotherapy alone and the first-generation EGFR-TKIs) and the afatinib group. The results showed that afatinib could improve PFS (HR: 0.58, 95% CI: 0.39-0.85, < 0.05) and ORR (OR = 2.86, 95% CI: 1.45-2.57, < 0.05), but had no benefit on OS (HR: 1.13, 95% CI: 0.15-8.75, > 0.05) and DCR (OR = 2.87, 95% CI: 0.97-8.48, > 0.05). For the safety of afatinib, the incidence of grade-3-and-above ARs was low (HR: 0.01, 95% CI: 0.00-0.02, < 0.05).
CONCLUSION
Afatinib improves the survival of NSCLC patients with brain metastases and shows satisfactory safety.
PubMed: 37228701
DOI: 10.1155/2023/5493725 -
Advanced Squamous Cell Carcinoma of the Lung: Current Treatment Approaches and the Role of Afatinib.OncoTargets and Therapy 2020Options for the treatment of squamous cell lung carcinoma expanded in recent years with the introduction of the immune checkpoint inhibitors into routine clinical... (Review)
Review
Options for the treatment of squamous cell lung carcinoma expanded in recent years with the introduction of the immune checkpoint inhibitors into routine clinical practice in both the first- and second-line settings but are still limited. As a result, pembrolizumab, given either alone or in combination with platinum-based chemotherapy, is now a standard first-line treatment for squamous cell lung cancer. However, few options exist once patients have progressed on immune checkpoint inhibitors and chemotherapy. In this setting, the irreversible ErbB family blocker, afatinib, has a potential role as second or subsequent therapy for some patients. The Phase III LUX-Lung 8 study demonstrated that afatinib significantly prolonged progression-free and overall survival compared with erlotinib in patients with squamous cell lung carcinoma. Notably, retrospective, ad-hoc biomarker analyses of a subset of patients from LUX-Lung 8 suggested that patients with ErbB family mutations derived particular benefit from afatinib, especially those with () mutations. Afatinib has a manageable and predictable safety profile, and adverse events can be managed with the use of a tolerability-guided dose modification protocol. Until more data are available, afatinib could be considered as a potential second-line treatment option for patients who have progressed on combined pembrolizumab and platinum-based chemotherapy and are ineligible for more established second-line options, or as a third-line option in patients who have received first-line immunotherapy, and second-line chemotherapy or chemotherapy and antiangiogenesis therapy. However, further data are required to support the use of afatinib following immunotherapy. Given that treatment options are limited in both of these settings, investigating an agent with an entirely new mechanism of action is warranted. If available, molecular analysis to identify ErbB family mutations or the use of proteomic profiling could help to further isolate patients who are likely to derive the most benefit from afatinib.
PubMed: 33061419
DOI: 10.2147/OTT.S250446 -
Cancers Jan 2022Treatment outcome between afatinib alone or with bevacizumab in non-small cell lung cancer (NSCLC) patient with epidermal growth factor receptor () mutation remains...
BACKGROUND
Treatment outcome between afatinib alone or with bevacizumab in non-small cell lung cancer (NSCLC) patient with epidermal growth factor receptor () mutation remains insufficiently reported.
METHODS
A total of 405 advanced NSCLC patients with sensitizing- mutation receiving first-line single-agent afatinib or with bevacizumab were grouped and propensity score-matched. Progression-free survival (PFS), overall survival (OS) and secondary T790M mutation were analyzed.
RESULTS
In the original cohort, 367 (90.6%) patients received afatinib treatment alone and 38 (9.4%) patients received afatinib plus bevacizumab. Patients who received bevacizumab combination were significantly younger (54.6 ± 10.9 vs. 63.9 ± 11.5; < 0.001) compared to the afatinib alone group. After propensity score matching, the afatinib alone and afatinib plus bevacizumab groups contained 118 and 34 patients, respectively. A non-significantly higher objective response was noted in the afatinib plus bevacizumab group (82.4% vs. 67.8%; = 0.133). In the propensity score-matched cohort, a bevacizumab add-on offered no increased PFS (16.1 vs. 15.0 months; = 0.500), risk reduction of progression (HR 0.85 [95% CI, 0.52-1.40]; = 0.528), OS benefit (32.1 vs. 42.0 months; = 0.700), nor risk reduction of death (HR 0.85 [95% CI, 0.42-1.74] = 0.660) compared to the single-agent afatinib. The secondary T790M rate in afatinib plus bevacizumab and afatinib alone groups was similar (56.3% vs. 49.4%, = 0.794). Multivariate analysis demonstrated that L858R (OR 0.51 [95% CI, 0.26-0.97]; = 0.044), uncommon mutation (OR 0.14 [95% CI, 0.02-0.64]; = 0.021), and PFS longer than 12 months (OR 2.71 [95% CI, 1.39-5.41]; = 0.004) were independent predictors of secondary T790M positivity.
CONCLUSION
Bevacizumab treatment showed moderate efficacy in real-world, afatinib-treated NSCLC patients with -sensitizing mutation.
PubMed: 35053480
DOI: 10.3390/cancers14020316 -
Thoracic Cancer Apr 2021Afatinib is an ErbB family blocker approved for the treatment of epidermal growth factor receptor mutation-positive nonsmall-cell lung cancer. A pivotal trial...
Afatinib is an ErbB family blocker approved for the treatment of epidermal growth factor receptor mutation-positive nonsmall-cell lung cancer. A pivotal trial demonstrated significant clinical benefits with manageable toxicity of afatinib as a second-line treatment option in squamous cell carcinoma of the lung (SCC) which led to approval in >60 countries. However, these results were derived from a controlled study conducted in selected patients and are not necessarily representative of the real-world use of this drug. In addition, data on afatinib use after immunotherapy in this clinical setting are lacking. The aim of this study is to evaluate the treatment outcomes and safety of afatinib as a second- or later-line treatment for SCC and to identify potential predictive biomarkers. As a real-world observational study, 130 eligible patients with advanced SCC, who progressed after platinum-based chemo- and immunotherapy, will be enrolled. Treatment outcomes and safety data will be collected for both the retrospective and prospective cohorts, and molecular profiling using tissue and plasma will be performed for the prospective cohort. The primary endpoint is time to treatment failure, and the secondary endpoints are objective response rate, progression-free survival, overall survival, and safety. Comparison of clinical outcomes with respect to the different programmed death-ligand 1 expression and molecular characteristics will also be carried out. This study will provide additional evidence on the usefulness of afatinib as a subsequent treatment, as well as feasible molecular biomarkers to predict its efficacy in this clinical setting.
Topics: Afatinib; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Female; Humans; Immunotherapy; Male; Prospective Studies; Retrospective Studies; Treatment Outcome
PubMed: 33586312
DOI: 10.1111/1759-7714.13880 -
BMC Cancer Feb 2024The irreversible epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) afatinib and dacomitinib are approved for first-line treatment of EGFR... (Observational Study)
Observational Study
The difference between dacomitinib and afatinib in effectiveness and safety in first-line treatment of patients with advanced EGFR-mutant non-small cell lung cancer: a real-world observational study.
OBJECTIVES
The irreversible epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) afatinib and dacomitinib are approved for first-line treatment of EGFR mutation-positive non-small cell lung cancer (NSCLC). We aimed to compare the efficacy and safety of afatinib and dacomitinib in this setting.
MATERIALS AND METHODS
Between September 2020 and March 2023, we retrospectively recruited patients diagnosed with advanced-stage EGFR-mutant NSCLC who were treated with first-line irreversible EGFR-TKIs. The enrolled patients were assigned to two groups based on whether they received afatinib or dacomitinib.
RESULTS
A total of 101 patients were enrolled in the study (70 to afatinib and 31 to dacomitinib). The partial response rates (PR) for first-line treatment with afatinib and dacomitinib were 85.7 and 80.6% (p = 0.522). The median progression-free survival (PFS) (18.9 vs. 16.3 months, p = 0.975) and time to treatment failure (TTF) (22.7 vs. 15.9 months, p = 0.324) in patients with afatinib and dacomitinib treatment were similar. There was no significant difference observed in the median PFS (16.1 vs. 18.9 months, p = 0.361) and TTF (32.5 vs. 19.6 months, p = 0.182) between patients receiving the standard dose and those receiving the reduced dose. In terms of side effects, the incidence of diarrhea was higher in the afatinib group (75.8% vs. 35.5%, p < 0.001), while the incidence of paronychia was higher in the dacomitinib group (58.1% vs. 31.4%, p = 0.004). The PFS (17.6 vs. 24.9 months, p = 0.663) and TTF (21.3 vs. 25.1 months, p = 0.152) were similar between patients younger than 75 years and those older than 75 years.
CONCLUSION
This study showed that afatinib and dacomitinib had similar effectiveness and safety profiles. However, they have slightly different side effects. Afatinib and dacomitinib can be safely administered to patients across different age groups with appropriate dose reductions.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Afatinib; Lung Neoplasms; Retrospective Studies; Protein Kinase Inhibitors; Treatment Outcome; ErbB Receptors; Mutation; Quinazolinones
PubMed: 38373960
DOI: 10.1186/s12885-024-11956-w -
BMC Cancer Nov 2022The optimal duration of anti-PD-1 for cancer therapy has not been tested, especially when using combination therapy. Epidermal growth factor receptor (EGFR) pathway...
OBJECTIVES
The optimal duration of anti-PD-1 for cancer therapy has not been tested, especially when using combination therapy. Epidermal growth factor receptor (EGFR) pathway blocker was the top compound that enhanced T-cell killing of tumor cells in a high-throughput immune-oncology screen, possibly by stimulate the antigen presentation machinery and other mechanisms. We explored the effect of combination of EGFR inhibition with a short course of anti-PD-1 therapy in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC).
METHOD
We analyzed the effect of a short course of anti-PD-1 with continuous afatinib on the survival of a real-world cohort of R/M HNSCC patients. Patient characteristics, treatments, efficacies, and toxicities were reviewed and recorded for analysis.
RESULTS
From November 2016 to May 2018, 51 consecutive patients received pembrolizumab and afatinib. The cutoff date was June 30, 2022. The most common toxicities (all grades) were diarrhea (62.7%), skin rash (43.1%), mucositis (31.4%), and paronychia (23.5%). The objective response rate was 54.9% (95% confidence interval [CI] 40.3-68.9%). Median progression-free survival was 5.9 months (95% CI: 4.4-7.6 months), and the median overall survival was 10.5 months (95% CI: 6.8-16.5 months). The 12-month, 24-month, 36-month, and 48-month survival rate was 47.0%, 22.5%, 17.7%, and 12.6% respectively.
CONCLUSIONS
This retrospective study showed that short course pembrolizumab with afatinib therapy has acceptable efficacy in R/M HNSCC patients. The durable response and long-term survival rates were similar to prospective clinical trials. Short course anti-PD-1 therapy, especially in combination with EGFR blocker, is worth for further prospective study.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Afatinib; Retrospective Studies; Data Analysis; Prospective Studies; Head and Neck Neoplasms; Carcinoma; ErbB Receptors
PubMed: 36443704
DOI: 10.1186/s12885-022-10343-7 -
Medicina (Kaunas, Lithuania) Sep 2021Patients who have advanced lung cancer and bone metastasis (BM) often suffer from skeletal-related events (SREs) that lead to poor quality of life and poor prognosis....
Patients who have advanced lung cancer and bone metastasis (BM) often suffer from skeletal-related events (SREs) that lead to poor quality of life and poor prognosis. Our study aimed to investigate the prognostic factors in patients with BM from epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma. This retrospective study included 77 lung adenocarcinoma patients with synchronous BM. These patients had first-line EGFR tyrosine kinase inhibitors (EGFR-TKIs) between January 2017 and December 2019. Among them, 42 patients were treated with 120 mg of subcutaneous denosumab monthly. We investigated their baseline characteristics, cancer management, SREs, progression-free survival (PFS), and overall survival (OS). The PFS in the patients treated with or without denosumab were 10.1 vs. 12.5 months ( = 0.971). The median OS was 26.9 vs. 29.5 months ( = 0.967) in no denosumab and denosumab groups, respectively. Univariate analyses showed benefit of afatinib in PFS and good performance status in OS. : Those patients that took afatinib as first-line EGFR-TKIs had significantly longer PFS than those treated with other TKIs. Denosumab had no prognostic effect on PFS or OS.
Topics: Adenocarcinoma of Lung; ErbB Receptors; Humans; Lung Neoplasms; Mutation; Prognosis; Protein Kinase Inhibitors; Quality of Life; Retrospective Studies
PubMed: 34577890
DOI: 10.3390/medicina57090967 -
Journal of Neuro-oncology Dec 2021Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. Amplification or overexpression of the epidermal growth factor receptor gene,...
BACKGROUND
Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. Amplification or overexpression of the epidermal growth factor receptor gene, part of the ErbB family, occur in approximately 40% and 60% of patients with GBM, respectively. We present data from a dose-finding study of the ErbB inhibitor afatinib in combination with radiotherapy (RT), with or without temozolomide (TMZ), in patients with GBM.
METHODS
This was a phase I, open-label, 3 + 3 dose-escalation trial in patients with newly-diagnosed, histologically-confirmed grade 4 malignant glioma and proven O-methylguanine-DNA methyltransferase gene promoter methylation status. The primary endpoint was the maximum tolerated dose (MTD) of continuous daily afatinib when given in combination with RT, with (regimen M) or without (regimen U) concomitant TMZ treatment.
RESULTS
Fifty-five patients were enrolled; 36 received ≥ 1 dose of trial medication (regimen M, n = 20, regimen U, n = 16). Afatinib was discontinued by all patients during the study. Reasons for afatinib discontinuation (regimen M/U) included disease progression (45%/50%), dose-limiting toxicity (10%/0%), and other adverse events (AEs; 35%/38%). The most frequently reported AEs with either regimen were diarrhea and rash, with no new safety signals identified. The MTD was determined as afatinib 30 mg in combination with daily TMZ and RT, and afatinib 40 mg in combination with RT alone.
CONCLUSIONS
This study identified the MTD for afatinib in combination with RT, with and without TMZ, in patients with GBM. Further studies of afatinib in patients with GBM are warranted and should be based on appropriate biomarker-based preselection.
TRIAL REGISTRATION
NCT00977431 (first posted September 15, 2009).
Topics: Adult; Afatinib; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Dacarbazine; Glioblastoma; Humans; Temozolomide; Treatment Outcome
PubMed: 34787778
DOI: 10.1007/s11060-021-03877-6 -
International Journal of Molecular... May 2023Non-small cell lung cancer (NSCLC) is a fatal malignant tumor with a high mortality rate. Cancer stem cells (CSCs) play pivotal roles in tumor initiation and...
Non-small cell lung cancer (NSCLC) is a fatal malignant tumor with a high mortality rate. Cancer stem cells (CSCs) play pivotal roles in tumor initiation and progression, treatment resistance, and NSCLC recurrence. Therefore, the development of novel therapeutic targets and anticancer drugs that effectively block CSC growth may improve treatment outcomes in patients with NSCLC. In this study, we evaluated, for the first time, the effects of natural cyclophilin A (CypA) inhibitors, including 23-demethyl 8,13-deoxynargenicin (C9) and cyclosporin A (CsA), on the growth of NSCLC CSCs. C9 and CsA more sensitively inhibited the proliferation of epidermal growth factor receptor (EGFR)-mutant NSCLC CSCs than EGFR wild-type NSCLC CSCs. Both compounds suppressed the self-renewal ability of NSCLC CSCs and NSCLC-CSC-derived tumor growth in vivo. Furthermore, C9 and CsA inhibited NSCLC CSC growth by activating the intrinsic apoptotic pathway. Notably, C9 and CsA reduced the expression levels of major CSC markers, including integrin α6, CD133, CD44, ALDH1A1, Nanog, Oct4, and Sox2, through dual downregulation of the CypA/CD147 axis and EGFR activity in NSCLC CSCs. Our results also show that the EGFR tyrosine kinase inhibitor afatinib inactivated EGFR and decreased the expression levels of CypA and CD147 in NSCLC CSCs, suggesting close crosstalk between the CypA/CD147 and EGFR pathways in regulating NSCLC CSC growth. In addition, combined treatment with afatinib and C9 or CsA more potently inhibited the growth of EGFR-mutant NSCLC CSCs than single-compound treatments. These findings suggest that the natural CypA inhibitors C9 and CsA are potential anticancer agents that suppress the growth of EGFR-mutant NSCLC CSCs, either as monotherapy or in combination with afatinib, by interfering with the crosstalk between CypA/CD147 and EGFR.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Cyclophilin A; Afatinib; Lung Neoplasms; Cell Line, Tumor; ErbB Receptors; Antineoplastic Agents; Neoplastic Stem Cells
PubMed: 37298389
DOI: 10.3390/ijms24119437 -
Journal of the Formosan Medical... Jan 2022Three first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are widely available to treat advanced lung adenocarcinoma harboring EGFR...
Comparing survival and subsequent treatment of first-line tyrosine kinase inhibitors in patients of advanced lung adenocarcinoma with epidermal growth factor receptor mutation.
BACKGROUND/PURPOSE
Three first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are widely available to treat advanced lung adenocarcinoma harboring EGFR mutation. However, studies comparing efficacy or effectiveness of these EGFR TKIs came out with inconclusive results.
METHODS
In this real-world data analysis with a nationwide retrospective cohort design, adult patients with newly diagnosed advanced lung adenocarcinoma with EGFR mutation between 2011 and 2016, who received a first-line EGFR TKI, were included. Overall survival (OS) and time to next treatment (TTNT) were compared between patients receiving different EGFR TKIs after overlap weighting.
RESULTS
We enrolled 10,431 patients, including 6,230, 2,359, and 1842 in gefitinib, erlotinib, and afatinib groups, respectively. The median (95% confidence interval [CI]) OS were 24.2 (22.9-26.2), 25.7 (24.0-27.9), and 29.1 (25.8-32.1) months for those receiving gefitinib, erlotinib, and afatinib, respectively (p = 0.001). The hazard ratios (95% CI) for the afatinib group were 0.85 (0.74-0.98) and 0.91 (0.79-1.05) comparing with the gefitinib and erlotinib groups, respectively. The median (95% CI) TTNT were 10.9 (10.4-11.2), 11.7 (11.3-12.1), 13.4 (12.5-14.3) months for those receiving gefitinib, erlotinib, and afatinib, respectively (p < 0.001). The hazard ratios (95% CI) for the afatinib group were 0.79 (0.70-0.88) and 0.89 (0.79-1.00) comparing with the gefitinib and erlotinib groups, respectively. There were 6111 (59%) patients receiving subsequent therapies, and the majority of them received a second-line chemotherapy, particularly platinum-based chemotherapy.
CONCLUSION
Afatinib, compared with gefitinib, might provide better effectiveness as the first-line targeted therapy for patients of advanced lung adenocarcinoma with EGFR mutation.
Topics: Adenocarcinoma of Lung; ErbB Receptors; Humans; Mutation; Protein Kinase Inhibitors; Retrospective Studies
PubMed: 33707140
DOI: 10.1016/j.jfma.2021.02.012