Purpose
We evaluated study outcomes in patients enrolled in Asian regions in the phase III EMBRACA trial of talazoparib vs. chemotherapy.
Materials and Methods
Patients with human epidermal growth factor receptor 2–negative germline BRCA1/2-mutated advanced breast cancer who received prior chemotherapy were randomized 2:1 to talazoparib 1 mg/day or chemotherapy (physician’s choice). Primary endpoint was progression-free survival (PFS) per independent central review in the intent-to-treat (ITT) population. This post-hoc analysis evaluated efficacy/safety endpoints in the ITT population of patients enrolled in Asian regions.
Results
Thirty-three patients were enrolled at Asian sites (talazoparib, n=23; chemotherapy, n=10). Baseline characteristics were generally comparable with the overall EMBRACA population. In Asian patients, median PFS was 9.0 months (95% confidence interval [CI] 3.0, 15.2) for talazoparib and 7.1 months (95% CI, 1.2, not reached) for chemotherapy (hazard ratio [HR] 0.74 [95% CI, 0.22, 2.44]). Objective response rate was numerically higher for talazoparib vs. chemotherapy (62.5% [95% CI, 35.4, 84.8] vs. 25.0% [95% CI, 3.2, 65.1]). Median overall survival was 20.7 months (95% CI, 9.4, 40.1) versus 21.2 months (95% CI, 2.7, 35.0) months (HR, 1.41 [95% CI, 0.49, 4.05]). In Asian patients, fewer grade 3/4 adverse events (AEs), serious AEs (SAEs), grade 3/4 SAEs, and AEs resulting in dose reduction/discontinuation occurred with talazoparib than chemotherapy; for talazoparib, the frequency of these events was lower in Asian patients versus overall EMBRACA population.
Conclusion
In this subgroup analysis, talazoparib numerically improved efficacy versus chemotherapy and was generally well tolerated in Asian patients, with fewer grade 3/4 TEAEs, SAEs, and TEAEs leading to dose modification vs. the overall EMBRACA population.
Citations
Citations to this article as recorded by
HR-positive/HER2-negative breast cancer arising in patients with or without BRCA2 mutation: different biological phenotype and similar prognosis Pu-Chun Li, Yi-Fan Zhu, Jia-Ni Pan, Qiao-Yan Zhu, Yu-Yang Liao, Xiao-Wen Ding, Lin-Feng Zheng, Wen-Ming Cao Therapeutic Advances in Medical Oncology.2024;[Epub] CrossRef
Detection and analysis of the safety profile of talazoparib based on FAERS database Mufei Tang, Peiyan Liu, Linzhe Du, Yuanyuan Li, Jinjin Chen, Yang Li Expert Opinion on Drug Safety.2024; : 1. CrossRef
Facing inevitable PARPis resistance: Mechanisms and therapeutic strategies for breast cancer treatment Haixia Liu, Xiaohui Chen, Yimin Jia, Hengyi Chen, Xiaohui Wang, Guoxiang Liu, Yang Luo Interdisciplinary Medicine.2023;[Epub] CrossRef
Sustained delivery of PARP inhibitor Talazoparib for the treatment of BRCA-deficient ovarian cancer Shicheng Yang, Allen Green, Needa Brown, Alexis Robinson, Merline Senat, Bryanna Testino, Daniela M. Dinulescu, Srinivas Sridhar Frontiers in Oncology.2023;[Epub] CrossRef
Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer S.-A. Im, A. Gennari, Y.H. Park, J.H. Kim, Z.-F. Jiang, S. Gupta, T.H. Fadjari, K. Tamura, M.Y. Mastura, M.L.T. Abesamis-Tiambeng, E.H. Lim, C.-H. Lin, A. Sookprasert, N. Parinyanitikul, L.-M. Tseng, S.-C. Lee, P. Caguioa, M. Singh, Y. Naito, R.A. Hukom, ESMO Open.2023; 8(3): 101541. CrossRef
Molecular Biology Mechanisms and Emerging Therapeutics of Triple-Negative Breast Cancer Zhiying Zhang, Rui Zhang, Donghai Li Biologics: Targets and Therapy.2023; Volume 17: 113. CrossRef
Development of the PARP inhibitor talazoparib for the treatment of advanced BRCA1 and BRCA2 mutated breast cancer Evthokia A. Hobbs, Jennifer K. Litton, Timothy A. Yap Expert Opinion on Pharmacotherapy.2021; : 1. CrossRef
Makoto Nishio, Dong-Wan Kim, Yi-Long Wu, Kazuhiko Nakagawa, Benjamin J. Solomon, Alice T. Shaw, Satoshi Hashigaki, Emiko Ohki, Tiziana Usari, Jolanda Paolini, Anna Polli, Keith D. Wilner, Tony Mok
Cancer Res Treat. 2018;50(3):691-700. Published online July 6, 2017
Purpose
Crizotinib has demonstrated superior progression-free survival (PFS) and objective response rates (ORRs) versus chemotherapy in previously treated and untreated patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC). We report the safety and efficacy of crizotinib in Asian subpopulations of two global phase III trials.
Materials and Methods
This analysis evaluated previously treated and untreated patients in two randomized, openlabel phase III trials of crizotinib versus chemotherapy in ALK-positive advanced NSCLC in second-line (PROFILE 1007) and first-line settings (PROFILE 1014). Efficacy and safety were analyzed by race in the intention-to-treat and “as-treated” populations for efficacy and safety endpoints, respectively.
Results
In previously treated (n=157) and untreated (n=157) Asian patients, PFS was statistically significantly longer with crizotinib versus chemotherapy (hazard ratio for PFS, 0.526; 95% confidence interval, 0.363 to 0.762; p < 0.001 and hazard ratio, 0.442; 95% confidence interval, 0.302 to 0.648; p < 0.001, respectively). Similar antitumor activity was seen in the non-Asian and overall populations. ORRs were statistically significantly higher with crizotinib versus chemotherapy in both Asian and non-Asian previously treated and untreated patients (p < 0.05). The most common treatment-emergent adverse events (any grade)with crizotinib were vision disorder, diarrhea, and nausea, which were observed at a comparable incidence across Asian and non-Asian populations, irrespective of previous treatment status. Most adverse events were mild to moderate in severity.
Conclusion
These data, currently the only analysis showing Asian and non-Asian populations in the same study, support the efficacy and safety of crizotinib in Asian patients with previously treated or untreated ALK-positive advanced NSCLC.
Long-Term Outcomes of Crizotinib Treated ALK-Positive Lung Cancer Patients: A Retrospective Audit of Prospective Data from Resource-Constrained Settings Akhil Kapoor, Vanita Noronha, Vijay Patil, Nandini Menon, Ravindra Nandhana, Amit Kumar, Abhishek Mahajan, Amit Janu, Rajiv Kumar, Kumar Prabhash South Asian Journal of Cancer.2023; 12(02): 179. CrossRef
Efficacy and Safety of Ceritinib 450 mg/day with Food and 750 mg/day in Fasted State in Treatment-Naïve Patients with ALK+ Non–Small Cell Lung Cancer: Results from the ASCEND-8 Asian Subgroup Analysis Byoung Chul Cho, Dong-Wan Kim, Ullas Batra, Keunchil Park, Sang-We Kim, Cheng-Ta Yang, Pei-Jye Voon, Virote Sriuranpong, K. Govind Babu, Khalid Amin, Yingbo Wang, Paramita Sen, Khemaies Slimane, Sarayut Geater Cancer Research and Treatment.2023; 55(1): 83. CrossRef
Successful Retreatment with Crizotinib After Crizotinib-Induced Liver Failure in ALK-Positive Advanced Lung Adenocarcinoma: A Case Report Xiangming Zhang, Kai Ni, Huijun Chen OncoTargets and Therapy.2023; Volume 16: 87. CrossRef
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Anaplastic Lymphoma Kinase Inhibitor-Induced Neutropenia: A Systematic Review Fabien Moinard-Butot, Simon Nannini, Cathie Fischbach, Safa Abdallahoui, Martin Demarchi, Thierry Petit, Laura Bender, Roland Schott Cancers.2023; 15(20): 4940. CrossRef
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Performance of Japanese patients in registrational studies Yasushi Goto, Sayaka Arakawa, Masayuki Shirasawa, Ryoko Higashiyama, Keisuke Baba, Ken Masuda, Yuki Shinno, Yuji Matsumoto, Yusuke Okuma, Tatsuya Yoshida, Hidehito Horinouchi, Noboru Yamamoto, Yuichiro Ohe Japanese Journal of Clinical Oncology.2022; 52(1): 53. CrossRef
Targeted therapy for advanced anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer Laird B Cameron, Nadia Hitchen, Elias Chandran, Tessa Morris, Renée Manser, Benjamin J Solomon, Vanessa Jordan Cochrane Database of Systematic Reviews.2022;[Epub] CrossRef
Targeted Extracellular Vesicles Delivered Verrucarin A to Treat Glioblastoma Kai Chen, Yingnan Si, Jia-Shiung Guan, Zhuoxin Zhou, Seulhee Kim, Taehyun Kim, Liang Shan, Christopher D. Willey, Lufang Zhou, Xiaoguang Liu Biomedicines.2022; 10(1): 130. CrossRef
The application of radiomics in predicting gene mutations in cancer Yana Qi, Tingting Zhao, Mingyong Han European Radiology.2022; 32(6): 4014. CrossRef
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Role ofSTK11inALK‑positive non‑small cell lung cancer (Review) Wen Zhou, Lu-Da Yan, Zhi-Qiong Yu, Na Li, Yong-Hua Yang, Meng Wang, Yuan-Yuan Chen, Meng-Xia Mao, Xiao-Chun Peng, Jun Cai Oncology Letters.2022;[Epub] CrossRef
Efficacy and Safety of Brigatinib Compared With Crizotinib in Asian vs. Non-Asian Patients With Locally Advanced or Metastatic ALK–Inhibitor-Naive ALK+ Non–Small Cell Lung Cancer: Final Results From the Phase III ALTA-1L Study Myung J. Ahn, Hye R. Kim, James C.H. Yang, Ji-Yu Han, Jacky Yu-Chung. Li, Maximilian J. Hochmair, Gee-Chen Chang, Angelo Delmonte, Ki H. Lee, Rosario G. Campelo, Cesare Gridelli, Alexander I. Spira, Raffaele Califano, Frank Griesinger, Sharmistha Ghosh, E Clinical Lung Cancer.2022; 23(8): 720. CrossRef
Secondary mutant ALK-I1171s in pituitary metastases from a patient with ALK fusion-positive advanced lung adenocarcinoma: A case report and literature review Dan Han, Kewei Zhao, Qin Yang, Liling Zhang, Shihong Fei Frontiers in Oncology.2022;[Epub] CrossRef
Combination of crizotinib and chemotherapy in patients with relapsed or refractory anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) Mei-ting Chen, Xiao-hong Fu, He Huang, Zhao Wang, Xiao-jie Fang, Yu-Yi Yao, Quan-Guang Ren, Ze-geng Chen, Tong-yu Lin Leukemia & Lymphoma.2021; 62(3): 571. CrossRef
Breakthrough in targeted therapy for non-small cell lung cancer Zhencong Ye, Yongmei Huang, Jianhao Ke, Xiao Zhu, Shuilong Leng, Hui Luo Biomedicine & Pharmacotherapy.2021; 133: 111079. CrossRef
Ceritinib Efficacy and Safety in Treatment-Naive Asian Patients With Advanced ALK-Rearranged NSCLC: An ASCEND-4 Subgroup Analysis Daniel S.W. Tan, Sarayut Geater, Chong-Jen Yu, Chun-Ming Tsai, Te-Chun Hsia, Jun Chen, Meng-Chih Lin, You Lu, Virote Sriuranpong, Cheng-Ta Yang, Paramita Sen, Fabrice Branle, Michael Shi, Yi-Long Wu JTO Clinical and Research Reports.2021; 2(3): 100131. CrossRef
Guidelines for clinical practice of ALK fusion detection in non-small-cell lung cancer: a proposal from the Chinese RATICAL study group Wenbin Li, Jing Zhang, Zhijie Wang, Lin Li, Jie Ma, Xiaoyang Zhou, Jie Wang, Zhiyong Liang, Jianming Ying Journal of the National Cancer Center.2021; 1(4): 123. CrossRef
Pathological cytomorphologic features and the percentage of ALK FISH-positive cells predict pulmonary adenocarcinoma prognosis: a prospective cohort study Fenge Jiang, Congcong Wang, Ping Yang, Ping Sun, Jiannan Liu World Journal of Surgical Oncology.2021;[Epub] CrossRef
Treatment of advanced non-small-cell lung cancer Kumar Prabhash, Amish Vora, Sewanti Limaye, Tarini Prasad Sahoo, Ullas Batra, Shekhar Patil, Vijay M. Patil, Vanita Noronha, Bharat Bhosale, Nirmal Vivek Raut, Narayanankutty Warrier, Bharat Vaswani, Govind Babu, Adwaita Gore, Nitesh Rohatgi, Shailesh Bon Cancer Research, Statistics, and Treatment.2021; 4(2): 279. CrossRef
Efficacy, safety, and biomarker analysis of ensartinib in crizotinib-resistant, ALK-positive non-small-cell lung cancer: a multicentre, phase 2 trial Yunpeng Yang, Jianya Zhou, Jianying Zhou, Jifeng Feng, Wu Zhuang, Jianhua Chen, Jun Zhao, Wei Zhong, Yanqiu Zhao, Yiping Zhang, Yong Song, Yi Hu, Zhuang Yu, Youling Gong, Yuan Chen, Feng Ye, Shucai Zhang, Lejie Cao, Yun Fan, Gang Wu, Yubiao Guo, Chengzhi The Lancet Respiratory Medicine.2020; 8(1): 45. CrossRef
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A Unique Case of a High-Grade Neuroepithelial Tumor With EML4-ALK Fusion in a Five-Month-Old Oliver D Mrowczynski, Russell Payne, Cunfeng Pu, Robert Greiner, Elias Rizk Cureus.2020;[Epub] CrossRef
Histomorphologic features of lung adenocarcinomas exhibiting ALK gene rearrangement Daniel S. Grosser, Haiying Zhang Baylor University Medical Center Proceedings.2019; 32(2): 206. CrossRef
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Emerging therapies for non-small cell lung cancer Chao Zhang, Natasha B. Leighl, Yi-Long Wu, Wen-Zhao Zhong Journal of Hematology & Oncology.2019;[Epub] CrossRef
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Front‐line treatment of ceritinib improves efficacy over crizotinib for Asian patients with anaplastic lymphoma kinase fusion NSCLC: The role of systemic progression control Shih‐Hao Huang, Allen Chung‐Cheng Huang, Chin‐Chou Wang, Wen‐Chen Chang, Chien‐Ying Liu, Stelios Pavlidis, Ho‐Wen Ko, Fu‐Tsai Chung, Ping‐Chih Hsu, Yi‐Ke Guo, Chih‐Hsi Scott Kuo, Cheng‐Ta Yang Thoracic Cancer.2019; 10(12): 2274. CrossRef
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Real-World Treatment Patterns, Survival, and Prediction of CNS Progression in ALK-Positive Non-Small-Cell Lung Cancer Patients Treated with First-Line Crizotinib in Latin America Oncology Practices Claudio Martín, Andrés F. Cardona, Zyanya Lucia Zatarain-Barrón, Alejandro Ruiz-Patiño, Omar Castillo, George Oblitas, Luis Corrales, Lorena Lupinacci, María Angelina Pérez, Leonardo Rojas, Lisde González, Luis Chirinos, Carlos Ortíz, Mauricio Lema, Carlo Oncology.2018; 94(5): 297. CrossRef
CRISPR therapeutic tools for complex genetic disorders and cancer (Review) Stella Baliou, Maria Adamaki, Anthony Kyriakopoulos, Demetrios Spandidos, Michalis Panagiotidis, Ioannis Christodoulou, Vassilis Zoumpourlis International Journal of Oncology.2018;[Epub] CrossRef