Drug combination shows long-term survival in advanced thymic cancer

Final results from the phase 2 PECATI clinical trial demonstrate encouraging long-term survival outcomes with the combination of lenvatinib and pembrolizumab in patients with previously treated advanced B3-thymoma and thymic carcinoma.

The findings, published in the Journal of Thoracic Oncology (JTO), the official journal of the International Association for the Study of Lung Cancer (IASLC), showed after a median follow-up of 24.6 months a median progression-free survival of 22.1 months and median overall survival of 40.2 months.

According to Dr. Jordi Remon from Department of Cancer Medicine at Gustave Roussy, Villejuif, (France), the results suggest that the combination may represent a potential treatment option for selected patients whose disease has progressed following platinum-based chemotherapy, although careful monitoring for treatment-related toxicities remains essential.

Thymic epithelial tumors are rare thoracic cancers that develop in the thymus, an organ located in the chest behind the breastbone. B3-thymoma and thymic carcinoma are among the most aggressive forms of these tumors. While platinum-based chemotherapy remains the standard initial treatment for advanced disease, there is no established standard second-line treatment when the cancer progresses.

The PECATI trial investigated whether combining lenvatinib, a multi-targeted tyrosine kinase inhibitor with antiangiogenic properties, and pembrolizumab, an immune checkpoint inhibitor, could provide sustained disease control in this difficult-to-treat population.

The multicenter, single-arm study enrolled 43 patients with metastatic B3-thymoma or thymic carcinoma who had experienced disease progression after at least one platinum-based chemotherapy regimen. Patients with pre-existing autoimmune disorders were excluded.

Participants received oral lenvatinib at 20 mg daily and intravenous pembrolizumab at 200 mg every three weeks, continuing until disease progression, unacceptable toxicity or completion of a maximum of 35 treatment cycles.

Of the 43 participants, 84% had thymic carcinoma and 16% had B3-thymoma. Nearly two-thirds had stage IVB disease, more than half had at least three metastatic sites, and approximately 44% had received two or more previous lines of treatment for advanced disease.

The final analysis demonstrated sustained clinical activity, building on earlier findings that established the study's primary endpoint.

Key results included:

• Median progression-free survival of 22.1 months, compared with 14.9 months reported in the study's earlier analysis.
• Median overall survival of 40.2 months, with 53% of patients alive at three years.
• An objective response rate of 25.6%, including one complete response. Median duration of responses, not reached, suggesting that responses were sustained in some patients
• A disease control rate of 93%, indicating that most patients experienced tumor shrinkage or stabilization.

Despite the encouraging efficacy findings, investigators emphasized the importance of proactive management of treatment-related adverse events. Grade 3 or higher treatment-related adverse events occurred in 44.2% of patients, and 27.9% discontinued at least one study drug because of treatment-related toxicity.

Immune-related adverse events occurred in 39.5% of patients, including serious cases of colitis, pneumonitis, myocarditis, encephalitis and liver toxicity. Two deaths occurred during the study that investigators considered unrelated to treatment.

The investigators concluded that the mature PECATI results provide additional evidence supporting the potential role of lenvatinib plus pembrolizumab in selected patients with previously treated advanced thymic tumors.

Dr. Remon cautioned that the study's relatively small sample size and single-arm design means the results cannot establish that the combination is superior to other treatments. The study also cannot determine the individual contribution of each drug to the observed outcomes.

Further prospective studies will be needed to determine the optimal treatment sequence, identify patients most likely to benefit and establish whether these combinations can improve outcomes while maintaining acceptable safety, Dr. Remon said.