Purpose The addition of immune checkpoint inhibitors to chemotherapy has improved survival outcomes in patients with extensive-stage small cell lung cancer (ES-SCLC). However, their real-world effectiveness remains unknown. Therefore, we investigated the effectiveness of atezolizumab plus chemotherapy in ES-SCLC in actual clinical settings.
Materials and Methods In this multicenter prospective cohort study, patients with ES-SCLC receiving or scheduled to receive atezolizumab in combination with etoposide and carboplatin were enrolled between June 2021 and August 2022. The primary outcomes were progression-free survival (PFS) and the 1-year overall survival (OS) rate.
Results A total of 100 patients with ES-SCLC were enrolled from seven centers. Median age was 69 years, and 6% had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2. The median PFS was 6.0 months, the 1-year OS rate was 62.2%, and the median OS was 13.5 months. An ECOG PS of 2-3 and progressive disease as the best response were poor prognostic factors for PFS, while an ECOG PS of 2-3 and brain metastasis were associated with poor prognosis for OS. In addition, consolidative thoracic radiotherapy was found to be an independent favorable prognostic factor for OS (hazard ratio, 0.336; p=0.021). Grade ≥ 3 treatment-related adverse events were observed in 7% of patients, with treatment-related deaths occurring in 2% of patients.
Conclusion We provided evidence of the favorable real-world effectiveness and safety of atezolizumab plus chemotherapy in ES-SCLC patients, including in the elderly and those with poor ECOG PS. Additional consolidative thoracic radiotherapy may also benefit ES-SCLC patients.
Purpose The mammalian target of rapamycin complex 1 (mTORC1) regulates cell growth and proliferation by growth factor coordination and amino acid availability. Leucyl-tRNA synthetase 1 (LARS1) senses the intracellular leucine concentration and mediates amino acid-induced activation of mTORC1. Thus, LARS1 inhibition could be useful in cancer treatment. However, the fact that mTORC1 can be stimulated by various growth factors and amino acids suggests that LARS1 inhibition alone has limitations in inhibiting cell growth and proliferation. We investigated the combined effects of BC-LI-0186, a LARS1 inhibitor, and trametinib, an MEK inhibitor, on non–small cell lung cancer (NSCLC).
Materials and Methods Protein expression and phosphorylation were observed by immunoblotting, and genes differentially expressed between BC-LI-0186–sensitive and –resistant cells were identified by RNA sequencing. The combined effect of the two drugs was inferred from the combination index values and a xenograft model.
Results LARS1 expression was positively correlated with mTORC1 in NSCLC cell lines. BC-LI-0186 treatment of A549 and H460 cells maintained in media supplemented with fetal bovine serum revealed paradoxical phosphorylation of S6 and activation of mitogen- activated protein kinase (MAPK) signaling. Compared with BC-LI-0186–sensitive cells, –resistant cells showed enrichment of the MAPK gene set. The combination of trametinib and BC-LI-0186 inhibited the phosphorylation of S6, MEK, and extracellular signal-regulated kinase and their synergistic effects were confirmed in a mouse xenograft model.
Conclusion The combination of BC-LI-0186 and trametinib inhibited the non-canonical mTORC1-activating function of LARS1. Our study demonstrated a new therapeutic approach for NSCLC without targetable driver mutations.
Citations
Citations to this article as recorded by
LARS1 is a Prognostic Biomarker and Exhibits a Correlation with Immune Infiltrates in Hepatocellular Carcinoma Longfei Fan, Zhongqiang Qin, Di Wu, Yunchuan Yang, Yigang Zhang, Bo Xie, Jingyu Qian, Jianzhu Wei, Zhaoying Wang, Peipei Yang, Zhen Qian, Mu Yuan, Ziyi Zhu, Yulin Tan, Yi Tan International Journal of General Medicine.2024; Volume 17: 2203. CrossRef
Personalizing Therapy Outcomes through Mitogen-Activated Protein Kinase Pathway Inhibition in Non-Small Cell Lung Cancer Hasan Alsharoh, Paul Chiroi, Ekaterina Isachesku, Radu Andrei Tanasa, Ovidiu-Laurean Pop, Radu Pirlog, Ioana Berindan-Neagoe Biomedicines.2024; 12(7): 1489. CrossRef
UCHL1 Overexpression Is Related to the Aggressive Phenotype of Non-small Cell Lung Cancer Chi Young Kim, Eun Hye Lee, Se Hyun Kwak, Sang Hoon Lee, Eun Young Kim, Min Kyoung Park, Yoon Jin Cha, Yoon Soo Chang Tuberculosis and Respiratory Diseases.2024; 87(4): 494. CrossRef
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
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
Citations to this article as recorded by
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
Purpose
The purpose of this study is to assess the role of adjuvant therapy in stage I-III gallbladder cancer (GBC) patients who have undergone R0 resection.
Materials and Methods
Clinical data were collected on 441 consecutive patients who underwent R0 resection for stage I-III GBC. Eligible patients were classified into adjuvant therapy and surveillance only groups. Propensity score matching (PSM) between the two groups was performed, adjusting clinical factors.
Results
In total, 84 and 279 patients treated with adjuvant therapy and followed up with surveillance only, respectively, were included in the analysis. Before PSM, the 5-year relapse-free survival (RFS) rate was lower in the adjuvant therapy group than in the surveillance only group (50.8% vs. 74.8%, p < 0.001), although there was no statistically significant difference in the 5-year overall survival (OS) rate (66.2% vs. 79.5%, p=0.089). After the PSM, baseline characteristics became comparable and there were no differences in the 5-year RFS (50.8% vs. 64.8%, p=0.319) and OS (66.2% vs. 70.4%, p=0.703) rates between the two groups.
Conclusion
The results suggest that fluoropyrimidine-based adjuvant therapy is not indicated in stage I-III GBC patients who have undergone R0 resection.
Citations
Citations to this article as recorded by
Prospective Randomized Controlled Trial Comparing Adjuvant Chemotherapy vs. No Chemotherapy for Patients with Carcinoma of Gallbladder Undergoing Curative Resection Sundeep Singh Saluja, Phani Kumar Nekarakanti, Pramod Kumar Mishra, Anurita Srivastava, Kishore Singh Journal of Gastrointestinal Surgery.2022; 26(2): 398. CrossRef
Adjuvant Therapy for Resectable Biliary Tract Cancer: A Bayesian Network Analysis Xiuqiong Chen, Fanqiao Meng, Hua Xiong, Yanmei Zou Frontiers in Oncology.2021;[Epub] CrossRef
Current standards and future perspectives in adjuvant treatment for biliary tract cancers Angela Lamarca, Julien Edeline, Mairéad G McNamara, Richard A Hubner, Masato Nagino, John Bridgewater, John Primrose, Juan W Valle Cancer Treatment Reviews.2020; 84: 101936. CrossRef
Prognostic factors and patterns of loco-regional failure in patients with R0 resected gallbladder cancer Jung Ho Im, Woo Jung Lee, Chang Moo Kang, Ho Kyoung Hwang, Jinsil Seong HPB.2020; 22(8): 1168. CrossRef
Prognostic Factors for Operated Gallbladder Cancer Bala Basak Oven Ustaalioglu, Ahmet Bilici, Mesut Seker, Umut Kefeli, Dincer Aydin, Serkan Celik, Tarik Demir, Burcak Erkol Journal of Gastrointestinal Cancer.2019; 50(3): 451. CrossRef
Role of Adjuvant Chemotherapy in Resected T2N0 Gall Bladder Cancer Abhay K. Kattepur, Shraddha Patkar, Mahesh Goel, Anant Ramaswamy, Vikas Ostwal Journal of Gastrointestinal Surgery.2019; 23(11): 2232. CrossRef
A systematic review of the effectiveness of adjuvant therapy for patients with gallbladder cancer Carlos Manterola, Galo Duque, Luis Grande, Xabier de Aretxabala, Roque Conejeros, Tamara Otzen, Nayely García HPB.2019; 21(11): 1427. CrossRef
Adjuvant Chemoradiotherapy is Associated with Improved Survival for Patients with Resected Gallbladder Carcinoma: A Systematic Review and Meta-analysis Byoung Hyuck Kim, Jeanny Kwon, Eui Kyu Chie, Kyubo Kim, Young Hoon Kim, Dong Wan Seo, Amol K. Narang, Joseph M. Herman Annals of Surgical Oncology.2018; 25(1): 255. CrossRef
Randomized clinical trial of adjuvant gemcitabine chemotherapy versus observation in resected bile duct cancer T Ebata, S Hirano, M Konishi, K Uesaka, Y Tsuchiya, M Ohtsuka, Y Kaneoka, M Yamamoto, Y Ambo, Y Shimizu, F Ozawa, A Fukutomi, M Ando, Y Nimura, M Nagino, S Nakamori, T Ajiki, H Baba, R Yamaguchi, M Kawai, H Nagano, F Miura, T Arai, Y Nishiwaki, S Kawasaki British Journal of Surgery.2018; 105(3): 192. CrossRef
Adjuvant systemic therapy and postoperative outcomes after resection of node positive gallbladder cancer Jiong-Jie Yu, Xin-Fei Xu, Tian Yang International Journal of Surgery.2018; 54: 307. CrossRef
The efficiency and regimen choice of adjuvant chemotherapy in biliary tract cancer Luxi Yin, Qi Xu, Jingjing Li, Qing Wei, Jieer Ying Medicine.2018; 97(50): e13570. CrossRef
Surgical Management of Gallbladder Cancer Gyulnara G. Kasumova, Omidreza Tabatabaie, Robert M. Najarian, Mark P. Callery, Sing Chau Ng, Andrea J. Bullock, Robert A. Fisher, Jennifer F. Tseng Annals of Surgery.2017; 266(4): 625. CrossRef