Complete pathologic response after concomitant pembrolizumab and radiotherapy in a patient with pretreated metastatic...

Thymic carcinoma (TC) is a rare and aggressive malignancy, accounting for approximately 6% of thymic neoplasms. Due to its frequent late-stage diagnosis and poor prognosis, standard treatment typically involves multimodal therapy, including platinum-based chemotherapy, radiotherapy, and surgery. However, effective treatment options remain limited, with response rates being unsatisfactory. Recent studies have highlighted the potential of immune checkpoint inhibitors (ICIs) in treating thymic epithelial tumors, particularly in tumors with high programmed cell death ligand 1 (PD-L1) expression. Despite this, the role of ICIs in TC is still under investigation, and further research is needed to assess their efficacy and safety in clinical practice.

We present the case of a 31-year-old male diagnosed with stage IVA squamous TC. Following disease progression after first-line chemotherapy with paclitaxel, carboplatin, and ramucirumab as part of the RELEVENT phase II trial, PD-L1 assessment revealed an 85% expression, leading to the initiation of off-label pembrolizumab (200 mg every 3 weeks). The patient subsequently developed oligoprogression with local sternal infiltration, prompting the addition of radiotherapy (10×3 Gy) alongside continued pembrolizumab. Over the following months, imaging demonstrated progressive response to treatment, culminating in a near-complete metabolic response. A residual mediastinal lesion was later surgically resected, revealing no viable tumor cells, indicative of a complete pathological response. Nine months after surgery, the patient is disease-free, with no reported immune-related adverse events.

This case highlights the potential of immune checkpoint inhibition combined with radiotherapy and surgery in the management of advanced TC. The patient's complete pathologic remission underscores the importance of a multidisciplinary approach. Further studies are warranted to establish ICIs as a standard treatment and optimize patient selection while mitigating immune-related toxicities.