Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFR-mutation-positive non-small-cell lung cancer after progression on first-line gefitinib (IMPRESS): a phase 3 randomised trial

Soria, Jean Charles; Wu, Yi‐Long; Nakagawa, Kazuhiko; Kim, Sang We; Yang, Jin; Ahn, Myung Ju; Wang, Jie; Yang, James Chih Hsin; Lü, You; Atagi, Shinji; Ponce, Santiago; Lee, Dong Hoon; Liu, Yunpeng; Yoh, Kiyotaka; Zhou, Jianying; Shi, Xiaojin; Webster, Alan; Jiang, Haiyi; Mok, Tony

doi:10.1016/s1470-2045(15)00121-7

Cited by 372 publications

(302 citation statements)

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“…The data of ORR was 18% and median PFS was 4.2 months for patients with chemotherapy alone in the previous study, but the hematologic and neurologic adverse effects were much more common in chemotherapy group (22). Considering the efficacy and toxicity, afatinib could be an optional choice compared with chemotherapy alone with much (23)(24)(25). Meanwhile, for advanced EGFRpositive patients with acquired resistance, changing to other 1st generation TKIs seemed to be the inefficient treatment.…”

Section: Discussionmentioning

confidence: 86%

The efficacy and toxicity of afatinib in advanced EGFR-positive non-small-cell lung cancer patients after failure of first-generation tyrosine kinase inhibitors: a systematic review and meta-analysis

et al. 2017

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Background: The first generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFRTKIs), gefitinib and erlotinib, have become the standard first-line treatment for non-small-cell lung cancer (NSCLC) patients with EGFR mutation. However, there was no pooled analysis focused on the usage of the second-generation TKI, afatinib, in advanced EGFR-positive NSCLC patients after failure of first generation TKIs. Therefore, a meta-analysis was conducted to solve the above question. Methods: Electronic databases were searched for eligible literatures. ORR (objective response rate), DCR (disease controlled rate), PFS (progression-free survival), OS (overall survival) and primary grade 3/4 adverse events were pooled with the corresponding 95% confidence interval using R software. Sensitivity analyses and heterogeneity were quantitatively evaluated. Results: A total of 545 EGFR-positive patients were available for analysis from five studies after detailed screening from 909 relevant studies. The pooled ORR and DCR of afatinib in EGFR-positive patients after failure of the first generation EGFR-TKIs were 0.12 (0.08-0.19) and 0.60 (0.53-0.68), respectively. Besides, the 6 m-PFS rate, 1 y-PFS rate and 6 m-OS rate were 0.26 (0.22-0.30), 0.08 (0.06-0.10) and 0.74 (0.56-0.86). The grade 3/4 rate of diarrhea and that of skin deformity were 0.23 (0.10-0.46) and 0.14 (0.05-0.33), respectively. Sensitivity analyses revealed similar results with lower heterogeneity. Conclusions: Considering the efficacy, toxicity and current availability, afatinib could be a therapeutic option for advanced EGFR mutated NSCLC patients after the failure of 1st-generation TKIs.

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Section: Discussionmentioning

confidence: 86%

The efficacy and toxicity of afatinib in advanced EGFR-positive non-small-cell lung cancer patients after failure of first-generation tyrosine kinase inhibitors: a systematic review and meta-analysis

et al. 2017

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“…The IMPRESS study (phase III) conducted in this article randomized patients progressed under the gefitinib treatment into cisplatin/pemetrexed or cisplatin/pemetrexed/gefitinib. Chemotherapy combined with gefitinib did not significantly contribute to survival (PFS: 5.4 months for both arms), concluding that platinum-based combined chemotherapy was the standard approach [20].…”

Section: Combining the Egfr-tki With Other Agentsmentioning

confidence: 93%

Treatment After First-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Resistance in Non- Small-Cell Lung Cancer

Kazaz

Öztop

2017

Turk Thorac J

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Systemic treatment is the basic treatment approach to advanced-stage non-small-cell lung cancer (NSCLC), and chemotherapy and targeted treatments are commonly employed in these patients. Recently, positive results achieved with immunotherapy have led to a growing number of treatment options and prolonged survival time. Today, specific tyrosine kinase inhibitors (TKIs), such as erlotinib, gefitinib, and afatinib, which target the epidermal growth factor receptor (EGFR), and the TKI crizotinib, which targets anaplastic lymphoma kinase gene rearrangement, have become the standard treatment among targeted therapies for patients with sensitive molecular anomalies. However, resistance develops against all these agents after a while. Numerous genetic mutations, T790M+ in particular, have been identified as resistance mechanisms against EGFR-TKIs, and researchers are developing specific inhibitors against them. Among those inhibitors, third-generation EGFR-TKIs such as osimertinib and rociletinib have gained prominence due to their high level of effectiveness and low toxicity profile. Besides, systemic chemotherapy and immunotherapy are proper alternatives. A second biopsy during the progression stage and better clarification of the mechanisms causing secondary resistance will enable more successful treatments in the future. KEYWORDS:Epidermal growth factor receptor, tyrosine kinase inhibitors, resistance, non-small-cell lung cancer INTRODUCTIONLung cancer is still the primary cause of cancer-related death for both sexes worldwide, causing approximately 1.4 million deaths every year [1]. Non-small-cell lung cancer (NSCLC) cases comprise approximately 80%-85% of all lung cancers. More than half of the NSCLC cases are advanced-stage at the time of diagnosis, and those patients are characterized by poor prognosis. Systemic chemotherapy has long been employed as the primary treatment approach for advanced-stage NSCLC. Despite a series of advances in chemotherapy and the application of histology-based approaches in the course of time, median survival time does not exceed 1 year [2]. On the other hand, recent discoveries of somatic mutations in NSCLC and the employment of specific inhibitors against them have led to significant changes in the treatment of advanced-stage NSCLC. Currently, there are two key oncogenic molecular anomalies reflected in routine practice: epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase gene rearrangement.Epidermal growth factor receptor mutations are observed in approximately 10% of the whole patient group, whereas this rate may go up to 40% among Asians, non-smokers, and in patients who have adenocarcinoma histology. Deletion at exon 19 and point mutation at exon 21 (L858R) are the most common EGFR mutations [3]. The presence of these mutations indicates sensitivity to EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib, gefitinib, and afatinib. The use of erlotinib and gefitinib (first-generation TKIs) and afatinib (second-generation TKIs) in first-, second-, a...

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“…For patients with active EGFR mutations, TKIs produced high response rates up to 75% and improved progression-free survival (PFS) to 9-13 months as compared with chemotherapy in randomized trials (4,(9)(10)(11). However, majority of the patients developed acquired drug resistance after initial response to TKI, and the median overall survival in those patients was estimated to 30 months.…”

Section: Historical and Current Perspectives Of Epidermal Growth Factmentioning

confidence: 99%

Management of non-small cell lung cancer with EGFR mutation: the role of radiotherapy in the era of tyrosine kinase inhibitor therapy—opportunities and challenges

Xia

Zhang

2017

J. Thorac. Dis.

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In recent years, the treatment of advanced non-small cell lung cancer (NSCLC) was greatly promoted by the discovery of oncogenic drivers and the development of targeted therapies specific for these drivers. Somatic mutations in epidermal growth factor receptor (EGFR) are the most common type in patients with NSCLC. Small-molecule tyrosine kinase inhibitor (TKI) targeting EGFR produced relatively high response rate and long duration with acceptable toxicity profile. Also, the life expectancy in patients with active EGFR mutation has been significantly prolonged than the past. Additionally, evolution of advanced imaging and radiation techniques has expanded the indications for radiotherapy in complex clinical situation. All of those factors contributed to the widely use of radiotherapy for advanced NSCLC treated with TKI therapy. In this review, we will discuss how to integrate radiotherapy into the comprehensive treatment of patients with TKI therapy in order to maximize the therapeutics effect.

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Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFR-mutation-positive non-small-cell lung cancer after progression on first-line gefitinib (IMPRESS): a phase 3 randomised trial

Cited by 372 publications

References 28 publications

The efficacy and toxicity of afatinib in advanced EGFR-positive non-small-cell lung cancer patients after failure of first-generation tyrosine kinase inhibitors: a systematic review and meta-analysis

The efficacy and toxicity of afatinib in advanced EGFR-positive non-small-cell lung cancer patients after failure of first-generation tyrosine kinase inhibitors: a systematic review and meta-analysis

Treatment After First-Generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Resistance in Non- Small-Cell Lung Cancer

Management of non-small cell lung cancer with EGFR mutation: the role of radiotherapy in the era of tyrosine kinase inhibitor therapy—opportunities and challenges

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