EGFR exon 20 insertion mutation in advanced thymic squamous cell carcinoma: Response to apatinib and clinical outcomes

Thymic carcinoma (TC) is a rare malignant tumor of the mediastinum with occult onset, rapid development, and poor prognosis. Surgery is the main treatment for early TC, but the majority of patients are diagnosed at Masaoka‐Koga stage III or IV with local invasion or distant metastasis. Platinum and anthracyclines are currently considered key components of first‐line chemotherapy for advanced TC; however, there are no standard treatment plans for patients who are refractory to first‐line and further chemotherapy. The clinical effect is also unsatisfactory. Apatinib has been successfully applied as third‐line treatment for advanced gastric cancer and has shown high efficacy in the treatment of various cancers, such as lung, liver, and colorectal cancers. Herein we report a case of advanced thymic squamous cell carcinoma harboring EGFR exon 20 insertion in which apatinib was administered after multi‐line chemotherapy and radiotherapy and a partial response was achieved after five months of treatment. To date, a five month overall response and 10 months of progression‐free survival have been achieved. Adverse reactions can be controlled and the patient's quality of life has improved. Apatinib provides a new option for clinicians to treat patients with advanced TC.

[1]  G. Giaccone,et al.  Pembrolizumab in patients with thymic carcinoma: a single-arm, single-centre, phase 2 study. , 2018, The Lancet. Oncology.

[2]  Huahao Shen,et al.  Effectiveness and safety of PD-1/PD-L1 inhibitors in the treatment of solid tumors: a systematic review and meta-analysis , 2017, Oncotarget.

[3]  Ying Cheng,et al.  Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients With Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction. , 2016, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  Gordon C Jayson,et al.  Antiangiogenic therapy in oncology: current status and future directions , 2016, The Lancet.

[5]  W. Fang,et al.  [Outcome of Nonsurgical Treatment for Locally Advanced Thymic Tumors]. , 2016, Zhongguo fei ai za zhi = Chinese journal of lung cancer.

[6]  T. Graeber,et al.  Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma. , 2016, The New England journal of medicine.

[7]  J. Taube,et al.  PD-1/PD-L1 inhibitors. , 2015, Current opinion in pharmacology.

[8]  R. West,et al.  Pemetrexed in patients with thymic malignancies previously treated with chemotherapy. , 2015, Lung cancer.

[9]  Y. Hosomi,et al.  Key components of chemotherapy for thymic malignancies: a systematic review and pooled analysis for anthracycline-, carboplatin- or cisplatin-based chemotherapy , 2014, Journal of Cancer Research and Clinical Oncology.

[10]  Yang Zhang,et al.  Prevalence, Clinicopathologic Characteristics, and Molecular Associations of EGFR Exon 20 Insertion Mutations in East Asian Patients with Lung Adenocarcinoma , 2014, Annals of Surgical Oncology.

[11]  T. Yoshino,et al.  The evaluation of immunohistochemical markers and thymic cortical microenvironmental cells in distinguishing thymic carcinoma from type b3 thymoma or lung squamous cell carcinoma. , 2013, Journal of clinical and experimental hematopathology : JCEH.

[12]  B Ribba,et al.  Theoretical investigation of the efficacy of antiangiogenic drugs combined to chemotherapy in xenografted mice. , 2013, Journal of theoretical biology.

[13]  S. Koch,et al.  Signal transduction by vascular endothelial growth factor receptors. , 2012, Cold Spring Harbor perspectives in medicine.

[14]  C. Moran,et al.  Thymic carcinoma, part 1: a clinicopathologic and immunohistochemical study of 65 cases. , 2012, American journal of clinical pathology.

[15]  T. Treasure,et al.  Rare thoracic cancers, including peritoneum mesothelioma. , 2012, European journal of cancer.

[16]  N. Girard Thymic Tumors: Relevant Molecular Data in the Clinic , 2010, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[17]  E. Engels Epidemiology of Thymoma and Associated Malignancies , 2010, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[18]  V. Rusch,et al.  Comparison of patterns of relapse in thymic carcinoma and thymoma. , 2009, The Journal of thoracic and cardiovascular surgery.

[19]  M. Raica,et al.  Immunohistochemical expression of vascular endothelial growth factor A (VEGF), and its receptors (VEGFR1, 2) in normal and pathologic conditions of the human thymus. , 2008, Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft.

[20]  W. Timens,et al.  Thymic epithelial tumours: a population-based study of the incidence, diagnostic procedures and therapy. , 2008, European journal of cancer.

[21]  S. Kohno,et al.  Thymic carcinoma with epidermal growth factor receptor gene mutations. , 2006, Lung cancer.

[22]  A. Dalgleish,et al.  VEGFr inhibitor YN968D1 xenograft dose response studies against human colon cancer Ls174t and HT29 , 2006 .