What is the evidence for using tislelizumab (anti-PD-1 monoclonal antibody) and lenvatinib (multi-kinase inhibitor) in treating unresectable thymoma?

Evidence for Tislelizumab and Lenvatinib in Unresectable Thymoma

There is no evidence supporting the use of tislelizumab for unresectable thymoma, and lenvatinib is not recommended for thymoma—it is specifically indicated for thymic carcinoma, not thymoma. This distinction is critical as these are separate disease entities with different treatment paradigms.

Key Distinction: Thymoma vs. Thymic Carcinoma

The question asks about thymoma, but the available evidence addresses thymic carcinoma. These are distinct pathologic entities requiring different treatment approaches 1.

Evidence for Lenvatinib

For Thymic Carcinoma (Not Thymoma)

Lenvatinib is a "Preferred" second-line systemic therapy option specifically for thymic carcinoma, not thymoma 1. The NCCN 2025 guidelines base this recommendation on:

• The REMORA trial: A phase 2 study of 42 patients with metastatic or recurrent thymic carcinoma showed an objective response rate of 38% with lenvatinib monotherapy 1, 2.

• Important caveat: The NCCN panel explicitly notes there is a risk for intolerable adverse effects with lenvatinib and dose reductions may be needed 1.

Emerging Combination Data

Lenvatinib plus pembrolizumab shows promise for B3 thymoma and thymic carcinoma 3. The PECATI trial (2025) demonstrated:

• 5-month progression-free survival of 88.4% in 43 patients with pretreated B3 thymoma (16%) and thymic carcinoma (84%) 3
• Grade 3 or worse immune-related adverse events occurred in 14% of patients, including myocarditis and encephalitis 3
• This combination is currently under investigation and not yet standard of care 4

Evidence for Tislelizumab

No evidence exists for tislelizumab in thymoma or thymic carcinoma. The guidelines and available literature do not mention tislelizumab as a treatment option for thymic epithelial tumors 1.

Treatment Recommendations for Unresectable Thymoma

For unresectable thymoma specifically (not thymic carcinoma), the evidence-based approach is:

First-Line Treatment

• Chemoradiotherapy (concurrent or sequential) is recommended for unresectable thymoma 1, 5
• Platinum-based chemotherapy regimens are standard 1
• Carboplatin/paclitaxel or cisplatin/etoposide can be used with radiation therapy 1

Second-Line Treatment

• Insufficient evidence exists to recommend routine use of targeted agents or immunotherapy for thymoma 1
• Platinum-based chemotherapy remains appropriate 1
• Octreotide alone or with corticosteroids may be reasonable for recurrent cases 1

Critical Safety Considerations

Immune checkpoint inhibitors carry significantly higher toxicity risks in thymic epithelial tumors compared to other malignancies 1:

• Pembrolizumab (the only PD-1 inhibitor with data) causes grade 3-4 myocarditis in 5-9% of thymic carcinoma patients, substantially higher than in other cancers 1
• Overall severe immune-related adverse events occur in 15% of patients 1
• Given these risks with pembrolizumab, extrapolating to tislelizumab (another anti-PD-1 antibody) would be inappropriate without specific safety data

Clinical Algorithm

For a patient presenting with unresectable thymoma:

1. Confirm pathology: Distinguish thymoma from thymic carcinoma, as treatment differs fundamentally 1

2. Multidisciplinary evaluation: Assess true unresectability with thoracic surgeons, as complete resection remains the most important prognostic factor 1

3. First-line treatment: Platinum-based chemoradiotherapy (concurrent preferred if tolerable) 1, 5

4. Avoid lenvatinib: This agent is not indicated for thymoma 1

5. Avoid tislelizumab: No evidence supports its use in thymic epithelial tumors

6. Second-line options: Continue platinum-based approaches or consider octreotide for recurrent disease 1