Phase II trial of gefitinib alone without radiation therapy for Japanese patients with brain metastases from EGFR-mutant lung adenocarcinoma

Iuchi, Toshihiko; Shingyoji, Masato; Sakaida, Tsukasa; Hatano, Kazuo; Nagano, Osamu; Itakura, Meiji; Kageyama, Hajime; Yokoi, Sana; Hasegawa, Yuzo; Kawasaki, Koichiro; Iwamoto, Toshihiko

doi:10.1016/j.lungcan.2013.08.016

Cited by 237 publications

(191 citation statements)

References 19 publications

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“…De novo CNS progression events were also lower with osimertinib than erlotinib/gefitinib (6 vs 15%) [10]. Several prospective studies have indicated that the first-generation TKIs, erlotinib and gefitinib, have clinical activity in patients with NSCLC and brain metastases, although there are limited data regarding direct intracranial activity [65,66]. These findings are consistent with observations that erlotinib and gefitinib can permeate the bloodbrain barrier, albeit inefficiently [67][68][69][70][71].…”

Section: Factors Influencing First-line Treatment Choice: Brain Metassupporting

confidence: 79%

Optimizing outcomes in EGFR Mutation-Positive Nsclc: Which Tyrosine Kinase Inhibitor and When?

Girard

2018

Future Oncol.

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Despite the efficacy of standard-of-care EGFR tyrosine kinase inhibitors (TKIs), erlotinib, gefitinib and afatinib, in EGFR mutation-positive non-small-cell lung cancer, resistance develops, most commonly due to the T790M mutation. Osimertinib showed clinical activity in the treatment of T790M-positive disease following progression on a first-line TKI, and is approved in this setting. Recently, osimertinib improved efficacy versus first-generation TKIs (erlotinib and gefitinib) in the first-line setting. Multiple factors can influence first-line treatment decisions, including subsequent therapy options, presence of brain metastases and tolerability, all of which should be considered in the long-term treatment plan. Further research into treatment sequencing is also needed, to optimize outcomes in EGFR mutation-positive non-small-cell lung cancer.

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Section: Factors Influencing First-line Treatment Choice: Brain Metassupporting

confidence: 79%

Optimizing outcomes in EGFR Mutation-Positive Nsclc: Which Tyrosine Kinase Inhibitor and When?

Girard

2018

Future Oncol.

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“…Drugs targeting mutated EGFR and anaplastic lymphoma kinase (ALK) genes have been highly effective when administered systemically (13,14). Several reports demonstrated that gefitinib or icotinib are associated with a favorable response in lung adenocarcinoma with BM, particularly in cases harboring EGFR mutations, such as our patient (15)(16)(17)(18)(19). EGFR-TKIs are reported to cross the blood-brain barrier, although it has been suggested that TKI concentration is reduced in the central nervous system compared with the serum levels (20).…”

Section: Discussionmentioning

confidence: 95%

Quick regression of brain metastases from lung adenocarcinoma with epidermal growth factor receptor-tyrosine kinase inhibitor treatment: A case report and literature review

Huang

Zhu

Wang

et al. 2016

Molecular and Clinical Oncology

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Abstract. Brain metastasis (BM) commonly occurs in patients with advanced lung cancer, and is associated with poor prognosis and limited treatment options, particularly for end-stage patients who are in poor physical and mental state. We herein present a case of lung adenocarcinoma with BM, as revealed by tumor marker and imaging studies. The patient was a 74-year-old woman who was diagnosed with lung adenocarcinoma with several metastatic lesions in the mediastinal lymph nodes, bone and brain. The patient underwent two cycles of chemotherapy, but the cancer recurred with enlarged BM, resulting in confusion and body dysfunction. The patient then received epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy with icotinib. After approximately 12 h of treatment the symptoms disappeared, and the metastatic lesions in the brain largely regressed in the following months. Our case indicates that the EGFR-TKI icotinib may provide a rapid and safe approach for emergency situations with BM from lung adenocarcinoma.

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“…No differences in survival were observed according to the used agents. Iuchi et al (25) reported a treatment response rate of 87.8% when gefitinib without radiation therapy was used for patients with brain metastasis from EGFR-mutant LAC. The median PFS and OS times of these patients were 14.5 and 21.9 months, respectively.…”

Section: Discussionmentioning

confidence: 99%

Icotinib combined whole brain radiotherapy for patients with brain metastasis from lung adenocarcinoma harboring epidermal growth factor receptor mutation

Zhang

2016

J. Thorac. Dis.

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Background: The brain is a metastatic organ that is most prone to lung adenocarcinoma (LAC). However, the prognosis of patients with brain metastasis remains very poor. In this study, we evaluated the efficacy of icotinib plus whole brain radiation therapy (WBRT) for treating patients with brain metastasis from epidermal growth factor receptor (EGFR)-mutated LAC. Methods: All patients received standard WBRT administered to the whole brain in 30 Gy in 10 daily fractions. Each patient was also instructed to take 125 mg icotinib thrice per day beginning from the first day of the WBRT. After completing the WBRT, maintenance icotinib was administered until the disease progressed or intolerable adverse effects were observed. Cranial progression-free survival (CPFS) and overall survival (OS) times were the primary endpoints. Results: A total of 43 patients were enrolled in this study. Two patients (4.7%) presented a complete response (CR), whereas 20 patients (46.5%) presented a partial response (PR). The median CPFS and OS times were 11.0 and 15.0 months, respectively. The one-year CPFS rate was 40.0% for the patients harboring EGFR exon 19 deletion and 16.7% for the patients with EGFR exon 21 L858R (P=0.027). Conclusions: The concurrent administration of icotinib and WBRT exhibited favorable effects on the patients with brain metastasis. EGFR exon 19 deletion was predictive of a long CPFS following icotinib plus WBRT.

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Phase II trial of gefitinib alone without radiation therapy for Japanese patients with brain metastases from EGFR-mutant lung adenocarcinoma

Cited by 237 publications

References 19 publications

Optimizing outcomes in EGFR Mutation-Positive Nsclc: Which Tyrosine Kinase Inhibitor and When?

Optimizing outcomes in EGFR Mutation-Positive Nsclc: Which Tyrosine Kinase Inhibitor and When?

Quick regression of brain metastases from lung adenocarcinoma with epidermal growth factor receptor-tyrosine kinase inhibitor treatment: A case report and literature review

Icotinib combined whole brain radiotherapy for patients with brain metastasis from lung adenocarcinoma harboring epidermal growth factor receptor mutation

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