Background Thymomas and thymic carcinomas (TC) are intrathoracic malignancies that, although rare, represent the most common anterior mediastinal tumors in adults (comprising approximately 0.2-1.5% of all malignancies).1 Recent accumulating evidence on immune checkpoint pathways suggests that immunotherapy might be a promising therapeutic option for refractory TCs.2 We herein report two cases of a pembrolizumab-treated TC patient.
Methods Immunotherapy is accessible through individual permission for the treatment of TC in Hungary. We retrospectively collected data of two TC patients treated with pembrolizumab in one institute.
Results The first patient was a 66-year-old woman. Squamous cell TC was diagnosed in her left parasternal region. She was a former smoker, had no history of autoimmune disorders, and had no associated symptoms at the time of diagnosis. She underwent open thymectomy. The histology proved type C (WHO classification) TC with a pathological TNM of T1aN0 and microscopic-positive margins. Consequently, the patient received 60 Gy of postoperative radiotherapy. Nine months after the surgery local recurrence and multiple hepatic metastases appeared. Six cycles of chemotherapy (ADOC regimen) were introduced as first-line systemic therapy which resulted in stable disease (SD) for 8 months. Pembrolizumab was administered as second-line treatment (200 mg every 3 weeks) for 6 cycles. The best result was SD. Due to progression, third-line docetaxel treatment was initiated. Shortly after, ptosis and diplopia developed. Myasthenia gravis was diagnosed, and third-line chemotherapy was judged ineffective. The second patient was a 63-year-old man. He was diagnosed with unresectable TC and treated with chemotherapy (ADOC regimen) up-front. After six cycles the tumor regressed, and surgery was performed with R2 result. Postoperatively, the patient was given six cycles of chemotherapy (cisplatin/etoposide) and radiotherapy. Six months later local progression was detected and pembrolizumab was commenced. Eight cycles of pembrolizumab produced SD as best response. No immune-related adverse effects (irAEs) were detected. After progression Sunitinib therapy was started. In both cases, additional immunohistochemistry investigations were performed.
Conclusions In the literature, there is no phase 3 trial on immune-checkpoint inhibitor (ICI) therapy of TC. Phase 2 trials reported promising results with pembrolizumab.3 4 However, there are conflicting results with other ICIs.5 Before starting, it is important to rule out autoimmune disorders to evade serious, even life-threatening immune-complications. The high likelihood of irAEs in TC also underpin the importance of predictive biomarkers. Further studies are required to evaluate the efficacy and safety of immunotherapy in TC.
Acknowledgements The authors thank the multidisciplinary clinical teams involved in the treatment and management of the patient.
Bushan K, Sharma S, Verma H. A review of thymic tumors. Indian Journal of Surgical Oncology 2013;4(2):112–116. https://doi.org/10.1007/s13193-013-0214-2
Isshiki T, Isobe K, Tochigi N, et al. Successful use of pembrolizumab to treat refractory thymic carcinoma with high PD-L1 expression. Case Rep Oncol2018;11(3):688–692. Published 2018 Oct 31. doi:10.1159/000493187
Giaccone G, Kim C, Thompson J, McGuire C, Kallakury B, Chahine JJ, et al. Pembrolizumab in patients with thymic carcinoma: a single-arm, single-centre, phase 2 study. Lancet Oncol 2018;19:247–255.
Cho J, Kim HS, Ku BM, Choi YL, Cristescu R, Han J, et al. Pembrolizumab for patients with refractory or relapsed thymic epithelial tumor: an open-label phase II trial. J Clin Oncol 2019;37(JCO2017773184):2162–2170.
Katsuya Y, Horinouchi H, Seto T, Umemura S, Hosomi Y, Satouchi M, et al. Single-arm, multicentre, phase II trial of nivolumab for unresectable or recurrent thymic carcinoma: PRIMER study. Eur J Cancer 2019;113:78e86.
This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.