Pembrolizumab in a Patient With Heavily Pre-Treated Squamous Cell Thymic Carcinoma and Cardiac Impairment: A Case Report and Literature Review

Abstract

Immunotherapy directed at the programmed cell death-1 receptor (PD-1) or its ligand PD-L1 has proven effective in solid malignancies such as melanoma, non-small cell lung cancer (NSCLC), urothelial cancer, renal cell carcinoma, and head and neck cancer. Compared with cytotoxic chemotherapy, radiotherapy, or molecular targeted agents, immunotherapy is an innovative strategy for treating malignancies, with durable clinical responses and manageable adverse events. Thymic carcinomas are extremely rare, constituting only 0.06% of all malignancies, are much more aggressive tumours than thymomas and have a worse prognosis. Nowadays, first line platinum-based chemotherapy for metastatic tumours are the cornerstone of treatment. However, the results of further therapeutic lines for metastatic or relapsed thymic carcinoma are unsatisfactory, with no regimen showing a consistent benefit. Moreover, the rarity of these tumours makes it difficult to carry out clinical trials. Herein we report a remarkable result of 1 year stable disease with good quality of life and no side effects obtained from the use of immunotherapy with pembrolizumab in a case of heavily pre-treated squamous cell thymic carcinoma and cardiac impairment. We also include a literature review of clinical trials on PD-1/PD-L1 inhibitors for the treatment of thymic epithelial cancers, taking a close look at cardiac toxicity.

Good Response of Advanced Thymic Carcinoma with Low PD-L1 Expression to Chemotherapy plus Pembrolizumab as First-Line Therapy and to Pembrolizumab as Maintenance Therapy: A Case Report

“…The patient is alive and has a more than 39 months survival time. This survival time is longer than previously reported cases of thymic carcinoma [13,14].…”

“…The patient is alive and has a more than 39 months survival time. This survival time is longer than previously reported cases of thymic carcinoma [13,14]. The present case was discussed by a multidisciplinary team that consisted of pulmonologists from our clinical department, radiologists, and thoracic surgeons to decide the most effective therapeutic approach for either type of tumor.…”

Perspective of Immune Checkpoint Inhibitors in Thymic Carcinoma

“…We found five case reports indicating the unique clinical course of patients with TC who received PD-1 blockade [ 14 , 15 , 16 , 17 , 18 ]. The summary of these case reports is displayed in Table 3 .…”

“…The duration of pembrolizumab and its combination therapy was 23 months. Cafaro et al described a case of heavily pretreated TC who was treated with pembrolizumab as the fourth-line treatment [ 15 ]. Uchida et al demonstrated an experience of nivolumab in four cases of unresectable TC [ 16 ].…”

Thymic epithelial tumors: examining the GTF2I mutation and developing a novel prognostic signature with LncRNA pairs to predict tumor recurrence

“…Therefore, once we find that a patient with advanced TET is GTF2I wild-type is diagnosed, indicating that the patient has a poor prognosis, better efficacy may be achieved by using PD-1, PD-L1, or CTLA4 inhibitors for treatment. Some previous studies have shown that anti-PD-L1 or anti-PD-1 antibodies such as pembrolizumab and avelumab can have a therapeutic effect on recurrent and metastatic advanced thymoma or thymic carcinoma and can control tumor growth [30][31][32]. We recommend that patients with advanced TETs should be tested for GTF2I gene mutation status, to more accurately predict patient prognosis and predict immune checkpoint inhibitor responses.…”