Cancer Research and Treatment

Original Articles

Lung and Thoracic cancer

Final Report on Real-World Effectiveness of Sequential Afatinib and Osimertinib in EGFR-Positive Advanced Non–Small Cell Lung Cancer: Updated Analysis of the RESET Study: Taeyun Kim, Tae Won Jang, Chang Min Choi, Mi-Hyun Kim, Sung Yong Lee, Yoon Soo Chang, Kye Young Lee, Seung Joon Kim, Sei Hoon Yang, Jeong Seon Ryu, Jeong Eun Lee, Shin Yup Lee, Chan Kwon Park, Sang Hoon Lee, Seung Hun Jang, Seong Hoon Yoon, Hyung-Joo Oh; Cancer Res Treat. 2023;55(4):1152-1170. Published online May 19, 2023; DOI: https://doi.org/10.4143/crt.2023.493

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Purpose
This study aimed to report the final analysis of time-on-treatment (TOT) and overall survival (OS) in patients with advanced-stage epidermal growth factor receptor (EGFR)+ non–small cell lung cancer (NSCLC) who received sequential afatinib and osimertinib and to compare the outcomes with other second-line regimens (comparator group).
Materials and Methods
In this updated report, the existing medical records were reviewed and rechecked. TOT and OS were updated and analyzed according to clinical features using the Kaplan-Meier method and log-rank test. TOT and OS were compared with those of the comparator group, in which most patients received pemetrexed-based treatments. A multivariable Cox proportional hazard model was used to evaluate features that could affect survival outcomes.
Results
The median observation time was 31.0 months. The follow-up period was extended to 20 months. A total of 401 patients who received first-line afatinib were analyzed (166 with T790M+ and second-line osimertinib, and 235 with unproven T790M and other second-line agents). Median TOTs on afatinib and osimertinib were 15.0 months (95% confidence interval [CI], 14.0 to 16.1) and 11.9 months (95% CI, 8.9 to 14.6), respectively. The median OS in the osimertinib group was 54.3 months (95% CI, 46.7 to 61.9), much longer than that in the comparator group. In patients who received osimertinib, the OS was longest with Del19+ (median, 59.1; 95% CI, 48.7 to 69.5).
Conclusion
This is one of the largest real-world studies reporting the encouraging activity of sequential afatinib and osimertinib in Asian patients with EGFR+ NSCLC who acquired the T790M mutation, particularly Del19+.

Citations

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KEAP1-NRF2 Pathway as a Novel Therapeutic Target for EGFR-Mutant Non-small Cell Lung Cancer
Jae-Sun Choi, Hye-Min Kang, Kiyong Na, Jiwon Kim, Tae-Woo Kim, Junyang Jung, Heejin Lim, Hyewon Seo, Seung Hyeun Lee
Tuberculosis and Respiratory Diseases.2025; 88(1): 138. CrossRef
A real-world cohort study of first-line afatinib in patients with EGFR-mutant advanced non-small cell lung cancer in Vietnam
Cam Phuong Pham, Thi Thai Hoa Nguyen, Anh Tu Do, Tuan Khoi Nguyen, Thi Anh Thu Hoang, Tuan Anh Le, Dinh Thy Hao Vuong, Dac Nhan Tam Nguyen, Van Khiem Dang, Thi Oanh Nguyen, Van Luan Pham, Minh Hai Nguyen, Thi Huyen Trang Vo, Hung Kien Do, Ha Thanh Vu, Thi
BMC Cancer.2024;[Epub] CrossRef
Real‐world evidence of brigatinib as second‐line treatment after crizotinib for ALK+ non‐small cell lung cancer using South Korean claims data (K‐AREAL)
Jeong Eun Lee, Jin Hyun Nam, Sun Hong Kwon, Bo Kyung Kim, Seung Min Ha
Cancer Medicine.2024;[Epub] CrossRef
Serum Concentrations of IGF-1R, ERK2, and EGFR and Their Clinical Significance in Patients with Neuroendocrine Tumors
Roksana Duszkiewicz, Janusz Strzelczyk, Elżbieta Chełmecka, Joanna Katarzyna Strzelczyk
Applied Sciences.2024; 14(16): 6998. CrossRef
Optimal first-line treatment for EGFR-mutated NSCLC: a comparative analysis of osimertinib and second-generation EGFR-TKIs
Hsu-Yuan Chen, Chia-Hung Chen, Wei-Chih Liao, Yu-Chao Lin, Hung-Jen Chen, Te-Chun Hsia, Wen-Chien Cheng, Chih-Yen Tu
BMC Pulmonary Medicine.2024;[Epub] CrossRef
Osimertinib as Second- and ≥Third-Line Treatment in Advanced and Recurrence EGFR-Mutant NSCLC Patients Harboring Acquired T790M Mutation
Mu-Han Peng, Yen-Hsiang Huang, Kuo-Hsuan Hsu, Jeng-Sen Tseng, Po-Hsin Lee, Kun-Chieh Chen, Gee-Chen Chang, Tsung-Ying Yang
Cancers.2024; 16(24): 4174. CrossRef
Effectiveness of first-line anticancer treatment may predict treatment response in further lines in stage III/IV patients with non-small cell lung cancer
Monika Bratova, Jana Skrickova, Magda Matusikova, Karolina Hrabcova, Libor Havel, Leona Koubkova, Michal Hrnciarik, Jana Krejci, Ondrej Fischer, Martin Svaton, Kristian Brat
Journal of Cancer Research and Clinical Oncology.2023; 149(19): 17123. CrossRef

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Real-World Study of Osimertinib in Korean Patients with Epidermal Growth Factor Receptor T790M Mutation–Positive Non–Small Cell Lung Cancer: Jang Ho Lee, Eun Young Kim, Cheol-Kyu Park, Shin Yup Lee, Min ki Lee, Seong-Hoon Yoon, Jeong Eun Lee, Sang Hoon Lee, Seung Joon Kim, Sung Yong Lee, Jun Hyeok Lim, Tae-Won Jang, Seung Hun Jang, Kye Young Lee, Seung Hyeun Lee, Sei Hoon Yang, Dong Won Park, Chan Kwon Park, Hye Seon Kang, Chang Dong Yeo, Chang-Min Choi, Jae Cheol Lee; Cancer Res Treat. 2023;55(1):112-122. Published online July 19, 2022; DOI: https://doi.org/10.4143/crt.2022.381

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Purpose
Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation–positive non–small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea.
Materials and Methods
Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints.
Results
A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects.
Conclusion
Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation–positive in Korean patients with no new safety signals.

Citations

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The importance of re-biopsy in the era of molecular therapy for lung cancer
Nensi Lalic, Daliborka Bursac, Marko Bojovic, Marko Nemet, Ivan Ergelasev
Srpski arhiv za celokupno lekarstvo.2024; 152(3-4): 209. CrossRef
Detection of EGFR exon 20 insertion mutations in non-small cell lung cancer: implications for consistent nomenclature in precision medicine
Jieun Park, Boram Lee, Ji-Young Song, Minjung Sung, Mi Jeong Kwon, Chae Rin Kim, Sangjin Lee, Young Kee Shin, Yoon-La Choi
Pathology.2024; 56(5): 653. CrossRef
Real‐world study of lazertinib as second‐line or greater treatment in advanced non‐small cell lung cancer
Jeong Uk Lim, Kyuhwan Kim, Kyu Yean Kim, Hye Seon Kang, Ah. Young Shin, Chang Dong Yeo, Sung Kyoung Kim, Chan Kwon Park, Sang Haak Lee, Seung Joon Kim
Thoracic Cancer.2024; 15(19): 1513. CrossRef
Comparative effectiveness of lazertinib in patients with EGFR T790M-positive non-small-cell lung cancer using a real-world external control
Ha-Lim Jeon, Meesong Kwak, Sohee Kim, Hye-Yeon Yu, Ju-Young Shin, Hyun Ae Jung
Scientific Reports.2024;[Epub] CrossRef
A Randomized, Multi-Center, Open Label Study to Compare the Safety and Efficacy between Afatinib Monotherapy and Combination Therapy with HAD-B1 for the Locally Advanced or Metastatic NSCLC Patients with EGFR Mutations
Eunbin Kwag, Soo-Dam Kim, Seong-Hoon Shin, Chulho Oak, So-Jung Park, Jun-Yong Choi, Seong Hoon Yoon, In-Cheol Kang, Mi-Kyung Jeong, Hyun Woo Lee, Sun-Hwi Bang, Ji Woong Son, Sanghun Lee, Seung Joon Kim, Hwa-Seung Yoo
Integrative Cancer Therapies.2024;[Epub] CrossRef
Clinical utility of repeated rebiopsy for EGFR T790M mutation detection in non-small cell lung cancer
Eun Hye Lee, Se Hyun Kwak, Kyeong Yeon Kim, Chi Young Kim, Sang Hoon Lee, Seok-Jae Heo, Yoon Soo Chang, Eun Young Kim
Frontiers in Oncology.2024;[Epub] CrossRef
Real-world evidence of osimertinib in Chinese patients with EGFR T790M-positive non-small cell lung cancer: a subgroup analysis from ASTRIS study
Qing Zhou, He-Long Zhang, Li-Yan Jiang, Yuan-Kai Shi, Yuan Chen, Jin-Ming Yu, Cai-Cun Zhou, Yong He, Yan-Ping Hu, Zong-An Liang, Yue-Yin Pan, Wen-Lei Zhuo, Yong Song, Gang Wu, Gong-Yan Chen, You Lu, Cui-Ying Zhang, Yi-Ping Zhang, Ying Cheng, Shun Lu, Chan
Journal of Cancer Research and Clinical Oncology.2023; 149(12): 10771. CrossRef

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Case Report

Bilateral Internal Auditory Canal Metastasis of Non-small Cell Lung Cancer: Chang-Hee Kim, Jung Eun Shin, Hee Joung Kim, Kye Young Lee; Cancer Res Treat. 2015;47(1):110-114. Published online August 28, 2014; DOI: https://doi.org/10.4143/crt.2013.079

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We report on a patient with brain metastasis involving bilateral internal auditory canal from non-small cell lung cancer (NSCLC). A 49-year-old woman who had been diagnosed with NSCLC (T2aN1M0) complained of persistent vertigo and bilateral tinnitus for three months. The patient had refused all treatments, including surgery and chemotherapy; however, she sought alternative medicine. The patient’s hearing loss showed rapid progression bilaterally, and rotatory vertigo with peripheral-type nystagmus developed. Magnetic resonance imaging of the brain showed irregular nodular enhancement within both internal auditory canals with leptomeningeal enhancement and multiple intracranial metastasis. The patient was treated with epidermal growth factor receptor-tyrosine kinase inhibitor, and the tumor showed partial response. This was a rare case of multiple brain metastases involving bilateral internal auditory canal from known NSCLC presenting with vertigo and hearing loss.

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Edith Vassallo, Andre-Stefan Gatt, Reuben Grech, Serena Capasso, Ferdinando Caranci, Lorenzo Ugga
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Direction-changing spontaneous nystagmus in cerebellopontine angle tumour
Hamin Jeong, Dong-Han Lee, Jung Eun Shin, Chang-Hee Kim
Journal of Clinical Neuroscience.2022; 95: 118. CrossRef
Ear and Labyrinth Toxicities Induced by Immune Checkpoint Inhibitors: A Disproportionality Analysis from 2014 to 2019
Fangyuan Hu, Xiaofei Ye, Yinghong Zhai, Jinfang Xu, Xiaojing Guo, Zhijian Guo, Xiang Zhou, Yiming Ruan, YongLong Zhuang, Jia He
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Review Article

Treatment of Non-small Cell Lung Carcinoma after Failure of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor: Jae Cheol Lee, Seung Hun Jang, Kye Young Lee, Young-Chul Kim; Cancer Res Treat. 2013;45(2):79-85. Published online June 30, 2013; DOI: https://doi.org/10.4143/crt.2013.45.2.79

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Since the first description of non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutation as a distinct clinical entity, studies have proved EGFR tyrosine kinase inhibitors (TKIs) as a first choice of treatment. The median response duration of TKIs as a first-line treatment for EGFR mutant tumors ranges from 11 to 14 months. However, acquired resistance to EGFR-TKIs is inevitable due to various mechanisms, such as T790M, c-Met amplification, activation of alternative pathways (IGF-1, HGF, PI3CA, AXL), transformation to mesenchymal cell or small cell features, and tumor heterogeneity. Until development of a successful treatment strategy to overcome such acquired resistance, few options are currently available. Here we provide a summary of the therapeutic options after failure of first line EGFR-TKI treatment for NSCLC.

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The clinicopathologic of pulmonary adenocarcinoma transformation to small cell lung cancer
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Histological transformation of adenocarcinoma to small cell carcinoma lung as a rare mechanism of resistance to epidermal growth factor receptor-tyrosine kinase inhibitors: Report of a case with review of literature
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Predictive Factors for Switched EGFR-TKI Retreatment in Patients with EGFR-Mutant Non-Small Cell Lung Cancer
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Original Article

Dexamethasone Inhibits TRAIL- and Anti-cancer Drugs-induced Cell Death in A549 Cells through Inducing NF-κB-independent cIAP2 Expression: Youn Seup Kim, Jae Seuk Park, Young Koo Jee, Kye Young Lee; Cancer Res Treat. 2004;36(5):330-337. Published online October 31, 2004; DOI: https://doi.org/10.4143/crt.2004.36.5.330

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Purpose

We have examined that dexamethasone inhibits apoptotic cell death of A549 lung epithelial cells through TRAIL and anti-cancer drugs. The purpose of the study is to determine the roles of GR, cIAP and NF-κB in this mechanism.

Materials and Methods

In the A549 lung epithelial cell line, TRAIL, taxol, doxorubicine & gemcitabine were used to investigate cell toxicity. Cells were pretreated 12 hours in advance with dexamethasone. RU486 was pretreated 30 minutes before dexamethasone. Crystal violet assay was used for cell toxicity tests. Apoptosis assay was performed by taking morphologic surveys with fluorescent microscopy after double staining with Hoechst 33342 & propium iodide. RT-PCR was used to investigate the gene expression of cIAP1 & cIAP2 by dexamethasone. Ad-IκB α-SR transduction study was used for the role of NF-κB.

Results

TRAIL and anti-cancer drug-induced apoptosis was partially suppressed in A549 cells pretreated with dexamethasone. The inhibitory effect on cell death disappeared in A549 cells pretreated with RU486. Using RT-PCR, changes of cIAP1 and cIAP2 genes manifestation in A549 cells subsequent to pretreatment with dexamethasone were examined. The results showed an increase in cIAP2 expression during a course of time which was suppressed by RU486 pretreatment. Induction of cIAP2 expression changes by dexamethasone was uniquely observed despite the blockade of NF-κB by Ad-IκBα-SR transduction.

Conclusions

These results suggest that dexamethasone inhibits TRAIL- and anti-cancer drug-induced apoptosis in A549 cells by inducing cIAP2 gene expression through a GR-mediated, NF-κB-independent pathway.

Citations

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Epigenetic and Glucocorticoid Receptor-Mediated Regulation of Glutathione Peroxidase 3 in Lung Cancer Cells
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