Mutations Predict for Poor Survival in Rearrangement Lung Adenocarcinoma Patients Treated with Crizotinib

Overview

Journal J Thorac Dis

Publisher AME Publishing Company

Specialty Pulmonary Medicine

Date 2018 Jul 13

PMID 29997966

Citations 18

Authors

Wen-Xian Wang

Chun-Wei Xu

Yan-Ping Chen

Wei Liu

Li-Hua Zhong

Fang-Fang Chen

Wu Zhuang

Yun-Jian Huang

Zhang-Zhou Huang

Rong-Rong Chen

Yan-Fang Guan

Xin Yi

Tang-Feng Lv

Wei-Feng Zhu

Jian-Ping Lu

Xiao-Jiang Wang

Yi Shi

Xian-Dong Lin

Gang Chen

Yong Song

Affiliations

Soon will be listed here.

Abstract

Background: Advanced non-small cell lung cancer (NSCLC) patients who harbor anaplastic lymphoma kinase () rearrangement are sensitive to an ALK inhibitor (crizotinib), but not all -positive patients benefit equally from crizotinib treatment. We analyze the impact of mutations on response to crizotinib in patients with rearrangement NSCLC.

Methods: Sixty-six rearrangement NSCLC patients receiving crizotinib were analyzed. 21 cases were detected successfully by the next generation sequencing validation FFPE before crizotinib. mutations were evaluated in 8 patients in relation to disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS) and overall survival (OS).

Results: mutations were observed in 2 (25.00%), 1 (12.50%), 1 (12.50%) and 4 (50.00%) patients in exons 5, 6, 7 and 8, respectively. The majority of patients were male (75.00%, 6/8), less than 65 years old (62.50%, 5/8) and never smokers (75.00%, 6/8). ORR and DCR for crizotinib in the entire case series were 61.90% and 71.43%, respectively. Statistically significant difference was observed in terms of PFS and OS between gene wild group and mutation group patients (P=0.038, P=0.021, respectively).

Conclusions: mutations reduce responsiveness to crizotinib and worsen prognosis in rearrangement NSCLC patients.

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References

Ma X, Le Teuff G, Lacas B, Tsao M, Graziano S, Pignon J . Prognostic and Predictive Effect of TP53 Mutations in Patients with Non-Small Cell Lung Cancer from Adjuvant Cisplatin-Based Therapy Randomized Trials: A LACE-Bio Pooled Analysis. J Thorac Oncol. 2016; 11(6):850-61. DOI: 10.1016/j.jtho.2016.02.002. View

Mogi A, Kuwano H . TP53 mutations in nonsmall cell lung cancer. J Biomed Biotechnol. 2011; 2011:583929. PMC: 3035360. DOI: 10.1155/2011/583929. View

Solomon B, Mok T, Kim D, Wu Y, Nakagawa K, Mekhail T . First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014; 371(23):2167-77. DOI: 10.1056/NEJMoa1408440. View

Siegel R, Miller K, Jemal A . Cancer Statistics, 2017. CA Cancer J Clin. 2017; 67(1):7-30. DOI: 10.3322/caac.21387. View

Deben C, Deschoolmeester V, Lardon F, Rolfo C, Pauwels P . TP53 and MDM2 genetic alterations in non-small cell lung cancer: Evaluating their prognostic and predictive value. Crit Rev Oncol Hematol. 2015; 99:63-73. DOI: 10.1016/j.critrevonc.2015.11.019. View

Zhang L, Jiang T, Li X, Wang Y, Zhao C, Zhao S . Clinical features of Bim deletion polymorphism and its relation with crizotinib primary resistance in Chinese patients with ALK/ROS1 fusion-positive non-small cell lung cancer. Cancer. 2017; 123(15):2927-2935. DOI: 10.1002/cncr.30677. View

Poeta M, Manola J, Goldwasser M, Forastiere A, Benoit N, Califano J . TP53 mutations and survival in squamous-cell carcinoma of the head and neck. N Engl J Med. 2007; 357(25):2552-61. PMC: 2263014. DOI: 10.1056/NEJMoa073770. View

Ettinger D, Wood D, Akerley W, Bazhenova L, Borghaei H, Camidge D . Non-Small Cell Lung Cancer, Version 6.2015. J Natl Compr Canc Netw. 2015; 13(5):515-24. DOI: 10.6004/jnccn.2015.0071. View

Steuer C, Ramalingam S . ALK-positive non-small cell lung cancer: mechanisms of resistance and emerging treatment options. Cancer. 2014; 120(16):2392-402. DOI: 10.1002/cncr.28597. View

10.

Doebele R, Pilling A, Aisner D, Kutateladze T, Le A, Weickhardt A . Mechanisms of resistance to crizotinib in patients with ALK gene rearranged non-small cell lung cancer. Clin Cancer Res. 2012; 18(5):1472-82. PMC: 3311875. DOI: 10.1158/1078-0432.CCR-11-2906. View

11.

Halvorsen A, Silwal-Pandit L, Meza-Zepeda L, Vodak D, Vu P, Sagerup C . TP53 Mutation Spectrum in Smokers and Never Smoking Lung Cancer Patients. Front Genet. 2016; 7:85. PMC: 4863128. DOI: 10.3389/fgene.2016.00085. View

12.

Katayama R, Shaw A, Khan T, Mino-Kenudson M, Solomon B, Halmos B . Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers. Sci Transl Med. 2012; 4(120):120ra17. PMC: 3385512. DOI: 10.1126/scitranslmed.3003316. View

13.

Wang W, Jiang X, Song Z, Zhang Y . Patients harboring EGFR mutation after primary resistance to crizotinib and response to EGFR-tyrosine kinase inhibitor. Onco Targets Ther. 2016; 9:211-5. PMC: 4712969. DOI: 10.2147/OTT.S97100. View

14.

Sullivan I, Planchard D . Treatment modalities for advanced ALK-rearranged non-small-cell lung cancer. Future Oncol. 2016; 12(7):945-61. DOI: 10.2217/fon.16.15. View

15.

Gainor J, Dardaei L, Yoda S, Friboulet L, Leshchiner I, Katayama R . Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK-Rearranged Lung Cancer. Cancer Discov. 2016; 6(10):1118-1133. PMC: 5050111. DOI: 10.1158/2159-8290.CD-16-0596. View

16.

Shaw A, Kim D, Nakagawa K, Seto T, Crino L, Ahn M . Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013; 368(25):2385-94. DOI: 10.1056/NEJMoa1214886. View

17.

Inamura K, Takeuchi K, Togashi Y, Hatano S, Ninomiya H, Motoi N . EML4-ALK lung cancers are characterized by rare other mutations, a TTF-1 cell lineage, an acinar histology, and young onset. Mod Pathol. 2009; 22(4):508-15. DOI: 10.1038/modpathol.2009.2. View

18.

Molina-Vila M, Bertran-Alamillo J, Gasco A, Mayo-de-Las-Casas C, Sanchez-Ronco M, Pujantell-Pastor L . Nondisruptive p53 mutations are associated with shorter survival in patients with advanced non-small cell lung cancer. Clin Cancer Res. 2014; 20(17):4647-59. DOI: 10.1158/1078-0432.CCR-13-2391. View

19.

Kwak E, Bang Y, Camidge D, Shaw A, Solomon B, Maki R . Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010; 363(18):1693-703. PMC: 3014291. DOI: 10.1056/NEJMoa1006448. View

20.

Deben C, Van den Bossche J, Van Der Steen N, Lardon F, Wouters A, Op de Beeck K . Deep sequencing of the TP53 gene reveals a potential risk allele for non-small cell lung cancer and supports the negative prognostic value of TP53 variants. Tumour Biol. 2017; 39(2):1010428317694327. DOI: 10.1177/1010428317694327. View