A Real-World Analysis of Patients with Untreated Metastatic Epidermal Growth Factor Receptor (EGFR)-Mutated Lung Adenocarcinoma Receiving First-Line Erlotinib and Bevacizumab Combination Therapy

Wang, Chin‐Chou; Chiu, Li-Chung; Tung, Pi-Hung; Kuo, Scott Chih‐Hsi; Chu, Chia-Hsun; Huang, Allen Chung-Cheng; Wang, Chih‐Liang; Chen, Chih‐Hung; Yang, Cheng‐Ta; Hsu, Ping‐Chih

doi:10.1007/s40487-021-00152-6

Cited by 5 publications

(13 citation statements)

References 47 publications

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“…Bevacizumab is an antiangiogenic agent that targets vascular endothelial growth factor (VEGF) and has been widely used in the treatment of advanced nonsquamous cell carcinoma. According to previous studies, when given in combination with EGFR-TKIs, including afatinib and erlotinib, bevacizumab has been shown to synergize with those EGFR-TKIs [32][33][34]. In addition, bevacizumab combined with EGFR-TKIs was shown to improve brain metastasis control and to reduce the occurrence of brain metastasis progression in patients with metastatic EGFR-mutated NSCLC [32][33][34].…”

Section: Discussionmentioning

confidence: 99%

“…According to previous studies, when given in combination with EGFR-TKIs, including afatinib and erlotinib, bevacizumab has been shown to synergize with those EGFR-TKIs [32][33][34]. In addition, bevacizumab combined with EGFR-TKIs was shown to improve brain metastasis control and to reduce the occurrence of brain metastasis progression in patients with metastatic EGFR-mutated NSCLC [32][33][34]. Therefore, bevacizumab combined with afatinib can be considered a therapeutic strategy for major uncommon EGFR-mutated lung adenocarcinoma in patients without the G719X mutation or in those with baseline brain and liver metastases.…”

Section: Discussionmentioning

confidence: 99%

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Afatinib in Untreated Stage IIIB/IV Lung Adenocarcinoma with Major Uncommon Epidermal Growth Factor Receptor (EGFR) Mutations (G719X/L861Q/S768I): A Multicenter Observational Study in Taiwan

et al. 2023

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Background Real-world clinical experience with afatinib as a treatment for advanced lung adenocarcinoma harboring uncommon epidermal growth factor receptor (EGFR) mutations (G719X, L861Q and S768I) has rarely been reported. Objective We aimed to perform a retrospective multicenter study to analyze afatinib therapy in untreated advanced lung adenocarcinoma harboring uncommon EGFR mutations. Patients and Methods Between May 2014 and June 2021, the data of 90 stage IIIB/IV lung adenocarcinoma patients with uncommon EGFR mutations (G719X/L861Q/S768I) treated with first-line afatinib from the cancer center database of Linkou, Tucheng, and Kaohsiung Chang Gung Memorial Hospitals were retrospectively retrieved and analyzed. Results Afatinib had an objective response rate (ORR) of 63.3% and a disease control rate (DCR) of 86.7%. The median progression-free survival (PFS) with first-line afatinib therapy was 17.3 months (95% confidence interval (CI), 12.07-22.53), and the median overall survival (OS) was 28.5 months (95% CI,) in all study patients. In the multivariate analysis, poor performance (Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2) and brain and liver metastases were independent predictors of unfavorable PFS. The G719X mutation (alone+compound) was an independent predictor of favorable PFS (hazard ratio (HR) = 0.578; 95% CI, 0.355−0.941; P = 0.027). Most afatinib-related adverse events (AEs) were limited to grades 1 and 2 and were manageable.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Afatinib in Untreated Stage IIIB/IV Lung Adenocarcinoma with Major Uncommon Epidermal Growth Factor Receptor (EGFR) Mutations (G719X/L861Q/S768I): A Multicenter Observational Study in Taiwan

et al. 2023

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“…In all previous clinical trials, bevacizumab was administered at a dose of 15 mg/kg, 13 – 15 , 17 , 19 which was different from most real-world clinical studies where bevacizumab was given at a dose of 7.5 mg/kg. 16 , 18 , 27 In a previous pivotal clinical trial (AVAiL trial), the efficacy of bevacizumab at doses of 15 or 7.5 mg/kg in combination with cisplatin plus gemcitabine chemotherapy was investigated in Asian patients with advanced non-squamous NSCLC. 38 , 39 Subgroup analysis of the AVAiL trial demonstrated that bevacizumab at a dose of 7.5 mg/kg was also as effective as a dose of 15 mg/kg in addition to chemotherapy for non-squamous NSCLC Asian patients.…”

Section: Discussionmentioning

confidence: 99%

Comparison of afatinib and erlotinib combined with bevacizumab in untreated stage IIIB/IV epidermal growth factor receptor-mutated lung adenocarcinoma patients: a multicenter clinical analysis study

et al. 2022

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Background: Although bevacizumab in combination with afatinib or erlotinib is an effective and safe first-line therapy for advanced epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC), there are very few clinical data comparing afatinib and erlotinib combined with bevacizumab. We performed a retrospective multicenter analysis for the comparison of two combination therapies. Methods: Between May 2015 and October 2020, data of 135 stage IIIB/IV EGFR-mutated NSCLC patients receiving first-line afatinib or erlotinib combined with bevacizumab combination therapy in Linkou, Keelung, Chiayi, and Kaohsiung Chang Gung Memorial Hospitals were retrieved and retrospectively analyzed. Results: In all, 67 patients received afatinib plus bevacizumab, and 68 patients received erlotinib plus bevacizumab. Afatinib combined with bevacizumab had an objective response rate (ORR) of 82.1% and a disease control rate (DCR) of 97.0%, and the ORR and DCR were 83.8 and 95.6%, respectively, in the erlotinib combined with bevacizumab group ( p = 0.798 and p = 1.000). The median progression-free survival was 20.7 and 20.3 months for the afatinib plus bevacizumab group and the erlotinib plus bevacizumab group, respectively [hazard ratio (HR) = 1.02; 95% confidence interval (CI), 0.891–1.953; p = 0.167). The overall survival was 41.9 and 51.0 months for the afatinib plus bevacizumab group and erlotinib plus bevacizumab group, respectively (HR = 1.42; 95% CI, 0.829–2.436; p = 0.201). The secondary EGFR-T790M mutation rates after disease progression were 44% in the afatinib plus bevacizumab group and 58.8% in the erlotinib plus bevacizumab group ( p = 0.165). Skin toxicity was the most frequent treatment-related adverse event (AE) in both treatment groups. Diarrhea, an AE, occurred significantly more frequently in the afatinib plus bevacizumab group than in the erlotinib plus bevacizumab group ( p < 0.05). Conclusion: Afatinib combined with bevacizumab was equally as effective as erlotinib combined with bevacizumab for untreated advanced EGFR-mutated NSCLC. Prospective clinical studies that explore bevacizumab combined with afatinib or erlotinib for advanced EGFR-mutated NSCLC are warranted.

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“…Aside from in combination with chemotherapy, bevacizumab plus targeted therapy often exhibits antitumor activity and yields clinical benefits in cancer patients. For example, erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has shown synergistic effects when combined with anti-VEGF therapies, mainly in patients with advanced non-small cell lung cancer and colorectal cancer [366][367][368][369][370]. Compared to erlotinib alone in EGFR-positive NSCLC patients, the combinational utilization of bevacizumab plus erlotinib brings clinical benefits to patients with the improvement of their progression-free survival (NCT02759614, NCT01562028) [371][372][373].…”

Section: Targeting Cancer Vasculaturementioning

confidence: 99%

Targeting the tumor stroma for cancer therapy

et al. 2022

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Tumors are comprised of both cancer cells and surrounding stromal components. As an essential part of the tumor microenvironment, the tumor stroma is highly dynamic, heterogeneous and commonly tumor-type specific, and it mainly includes noncellular compositions such as the extracellular matrix and the unique cancer-associated vascular system as well as a wide variety of cellular components including activated cancer-associated fibroblasts, mesenchymal stromal cells, pericytes. All these elements operate with each other in a coordinated fashion and collectively promote cancer initiation, progression, metastasis and therapeutic resistance. Over the past few decades, numerous studies have been conducted to study the interaction and crosstalk between stromal components and neoplastic cells. Meanwhile, we have also witnessed an exponential increase in the investigation and recognition of the critical roles of tumor stroma in solid tumors. A series of clinical trials targeting the tumor stroma have been launched continually. In this review, we introduce and discuss current advances in the understanding of various stromal elements and their roles in cancers. We also elaborate on potential novel approaches for tumor-stroma-based therapeutic targeting, with the aim to promote the leap from bench to bedside.

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A Real-World Analysis of Patients with Untreated Metastatic Epidermal Growth Factor Receptor (EGFR)-Mutated Lung Adenocarcinoma Receiving First-Line Erlotinib and Bevacizumab Combination Therapy

Cited by 5 publications

References 47 publications

Afatinib in Untreated Stage IIIB/IV Lung Adenocarcinoma with Major Uncommon Epidermal Growth Factor Receptor (EGFR) Mutations (G719X/L861Q/S768I): A Multicenter Observational Study in Taiwan

Afatinib in Untreated Stage IIIB/IV Lung Adenocarcinoma with Major Uncommon Epidermal Growth Factor Receptor (EGFR) Mutations (G719X/L861Q/S768I): A Multicenter Observational Study in Taiwan

Comparison of afatinib and erlotinib combined with bevacizumab in untreated stage IIIB/IV epidermal growth factor receptor-mutated lung adenocarcinoma patients: a multicenter clinical analysis study

Targeting the tumor stroma for cancer therapy

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