Long-term disease stabilization with lenvatinib in advanced thymic carcinoma: A case report

Abstract

Lenvatinib, a multi-kinase inhibitor, has shown promising activity in unresectable thymic carcinoma, but long-term real-world data are scarce. We describe a 72-year-old woman with Masaoka stage IVb thymic squamous cell carcinoma who experienced disease progression after ADOC chemotherapy and multiple courses of thoracic radiotherapy. Lenvatinib was initiated at 24 mg/day and reduced to 8 mg/day because of hypertension, hemoptysis, and hypothyroidism. The patient achieved 23 months of disease stabilization before sudden death at home. Postmortem imaging suggested acute exacerbation of interstitial pneumonia. This case highlights the potential of lenvatinib to achieve prolonged disease control even at reduced doses and underscores the need for careful pulmonary monitoring in patients with prior thoracic irradiation.

Introduction

Thymic carcinoma is a rare and aggressive malignancy arising from thymic epithelial cells, accounting for less than 1% of all mediastinal tumors. Optimal treatment strategies for advanced or recurrent disease remain poorly defined. Platinum-based chemotherapy regimens such as ADOC (cisplatin, doxorubicin, vincristine, and cyclophosphamide) are commonly used first-line; however, disease progression is frequent and effective second-line therapies are limited.^1–5

Lenvatinib, a multi-tyrosine kinase inhibitor targeting VEGFR, FGFR, PDGFR, and RET, demonstrated a disease control rate of 95% in a phase II trial in Japan, leading to its approval in 2021 for advanced or unresectable thymic carcinoma. Nevertheless, data on long-term real-world efficacy and safety, especially in patients with prior thoracic radiotherapy, remain scarce.

Here we report a case of advanced thymic squamous cell carcinoma treated with lenvatinib following chemotherapy failure and repeated thoracic radiotherapy. The patient achieved disease stabilization for 23 months despite dose reduction, and ultimately died of presumed acute exacerbation of interstitial pneumonia. This case illustrates both the therapeutic potential and the pulmonary risks of lenvatinib in heavily pretreated patients.

Case presentation

A 72-year-old Japanese woman with no smoking history was incidentally found to have an anterior mediastinal mass and multiple pulmonary nodules on routine chest computed tomography (CT). Contrast-enhanced CT revealed a 60 × 30 mm anterior mediastinal mass (Figure 1(a)) and bilateral pulmonary nodules (Figure 1(b)). Fluorodeoxyglucose positron emission tomography (FDG-PET) showed increased uptake in the mediastinal mass (SUVmax 4.6–4.9) (Figure 1(c)). CT-guided biopsy confirmed thymic squamous cell carcinoma, Masaoka stage IVb, TNM stage T4N0M1b. Arrows indicate tumor lesions.

Figure 1.

Initial imaging at diagnosis. (a) Contrast-enhanced chest CT showing a 60 × 30 mm anterior mediastinal mass (mediastinal window). Arrows indicate tumor lesions. (b) Chest CT (lung window) demonstrating multiple nodules in both lungs. Arrows indicate tumor lesions. (c) FDG-PET scan showing increased uptake in the anterior mediastinal mass Arrows indicate tumor lesions (SUVmax 4.6–4.9). Arrows indicate tumor lesions.

The patient initially sought second opinions and underwent repeated thoracic radiotherapy at a specialized center: 51 Gy to the mediastinum and 40 Gy to the left chest wall over 1 year. Several months later she developed progressive dyspnea and bilateral pleural effusions. Imaging revealed increased pleural fluid and disseminated nodular lesions. Two cycles of ADOC chemotherapy were administered (cisplatin 50 mg/m², doxorubicin 40 mg/m², vincristine 0.6 mg/m², cyclophosphamide 700 mg/m²), but disease progression ensued.

Given the absence of effective second-line options and the patient’s declining performance status (ECOG 2), lenvatinib was started at 24 mg/day. Within 2 weeks, grade 2 hypertension, epistaxis, hemoptysis, and hypothyroidism occurred. Dose reductions were implemented stepwise to 8 mg/day, maintained thereafter. Levothyroxine and antihypertensives were prescribed. Dose adjustments were based on individualized clinical judgment.

Serial CT scans every 2–3 months showed stable disease for 18 months (Figure 2(a) and (b)). At 23 months, gradual progression of pleural dissemination and mediastinal tumor enlargement was seen (Figure 3). One month later the patient was found collapsed at home and pronounced dead upon arrival at the emergency department. Postmortem non-contrast chest CT revealed bilateral diffuse interstitial infiltrates and increased tumor burden (Figure 4). No autopsy was performed. The disease remained stable for approximately 18 months after the initiation of lenvatinib therapy.

Figure 2.

Pre- and post-treatment findings. (a) Chest CT before lenvatinib initiation showing disseminated pulmonary nodules and bilateral pleural effusions (arrow indicates a metastatic lesion in the left lung). Arrows indicate tumor lesions. (b) Chest CT after 3 months of lenvatinib therapy showing stable pulmonary nodules with no significant progression. Arrows indicate tumor lesions. Arrows indicate tumor lesions.

Figure 3.

Disease status at 23 months after lenvatinib initiation. CT images reveal gradual progression of pleural dissemination and mild enlargement of the mediastinal mass. Arrows indicate tumor lesions. Arrows indicate tumor lesions.

Figure 4.

Postmortem imaging. Chest CT at emergency department arrival shows diffuse bilateral interstitial infiltrates consistent with acute exacerbation of interstitial pneumonia, along with increased tumor burden. Arrows indicate tumor lesions. Arrows indicate tumor lesions.

However, follow-up imaging at 23 months demonstrated progression with increasing pleural and mediastinal disease. The death certificate listed acute exacerbation of interstitial pneumonia as the primary cause of death. Arrows indicate tumor lesions.

Key laboratory values during lenvatinib therapy showed no significant hematologic or biochemical abnormalities aside from mild thyroid dysfunction.

Written informed consent for publication of clinical data and images was obtained from the patient’s legally authorized representative after the patient’s death.”

Discussion

This case demonstrates long-term disease stabilization—23 months—with lenvatinib in advanced thymic carcinoma after chemotherapy and repeated thoracic radiotherapy. Importantly, disease control was maintained despite reduction of the lenvatinib dose to one-third of the standard starting dose. This aligns with previous reports that lenvatinib retains antitumor activity even at reduced doses, likely due to its multi-targeted antiangiogenic effects.

The presumed cause of death was acute exacerbation of interstitial pneumonia, based on postmortem CT findings. Although lenvatinib-induced interstitial lung disease (ILD) is rare, it has been reported, particularly in patients with prior thoracic irradiation. The combination of previous radiation-induced lung injury and VEGF-inhibition may have contributed to pulmonary toxicity. A radiation recall phenomenon cannot be excluded.

This case underscores two important points: (1) lenvatinib can achieve prolonged disease control in heavily pretreated thymic carcinoma even at reduced doses; and (2) vigilant pulmonary monitoring is essential in patients with prior thoracic irradiation who receive VEGF-targeted therapy. This long-term response suggests that lenvatinib can achieve prolonged disease control even at a reduced dose.

Limitations include the absence of autopsy, which prevents definitive attribution of cause of death, and the inherent limitation of single-case generalizability.

Conclusion

Lenvatinib achieved nearly 2 years of disease stabilization in advanced thymic carcinoma following chemotherapy failure, despite dose reductions. Clinicians should consider lenvatinib as a salvage option in similar patients, while exercising caution and close monitoring for pulmonary complications in those with prior thoracic irradiation.