Transforming thymic carcinoma treatment with a dual approach

Thymic epithelial tumors are a rare group of malignancies originating in the thymus gland, that includes thymoma and thymic carcinoma. Among these, thymic carcinoma is the more aggressive subtype, characterized by high invasiveness, metastatic potential, and poor prognosis. With an incidence of just 0.15 cases per 100,000 person-years, its rarity poses significant challenges for treatment development. While platinum-based chemotherapy remains the current standard of care, its efficacy is limited. Immune checkpoint inhibitors have shown promise in pretreated cases, but durable and effective systemic therapies for chemotherapy-naïve patients remain a critical unmet need.

To address this, a team of researchers led by Associate Professor Takehito Shukuya from the Department of Respiratory Medicine, Juntendo University, Japan along with Dr. Tetsuhiko Asao, Dr. Tomoyasu Mimori, and Prof. Kazuhisa Takahashi from Juntendo University, Japan,

conducted the MARBLE study to evaluate the combination of atezolizumab, an immune checkpoint inhibitor, with carboplatin and paclitaxel in patients with advanced or recurrent thymic carcinoma. The findings of the study were published on 03 March 2025 in Volume 26, Issue 3 of The Lancet Oncology.

This multicenter, single-arm, phase II clinical trial was conducted across 15 hospitals in Japan and enrolled 48 patients with histologically confirmed advanced or recurrent thymic carcinoma. During the induction phase, patients received a combination of atezolizumab, carboplatin, and paclitaxel every three weeks for up to six cycles. Those with non-progressive disease transitioned to a maintenance phase, receiving atezolizumab every three weeks for up to two years.

Dr. Shukuya explains, “The MARBLE study delivered promising results. With a median follow-up of 15.3 months, the combination therapy achieved an objective response rate of 56% and a median progression-free survival (PFS) of 9.6 months, outperforming historical chemotherapy outcomes. The disease control rate reached 98%, with 56% of patients achieving partial responses and 42% maintaining stable disease.”

The safety profile was consistent with the known effects of atezolizumab, carboplatin, and paclitaxel, with no new safety concerns or treatment-related deaths. Adverse events were manageable, with the most common severe events being neutropenia, leukopenia, maculopapular rash, and febrile neutropenia. Notably, patients with higher programmed cell death ligand 1 expression on tumor or immune cells exhibited longer PFS, highlighting its potential as a predictive biomarker for treatment response.

The MARBLE study presents a promising therapeutic option for advanced thymic carcinoma, combining immune checkpoint inhibitors with platinum-based chemotherapy. Dr. Shukuya says, “The combination of regimen delivers durable tumor responses and prolonged disease control with manageable safety, positioning it as a potential new standard of care. With these favorable results, approval for insurance coverage in Japan and globally, is anticipated.”

Overall, the MARBLE study highlights the potential of atezolizumab combined with carboplatin and paclitaxel as an effective and well-tolerated treatment option for advanced thymic carcinoma. This regimen addresses the therapeutic gap in this rare and challenging disease, offering hope for improved outcomes and long-term disease control for affected patients.

Reference

About Associate Professor Takehito Shukuya

Dr. Takehito Shukuya is an Associate Professor in the Department of Respiratory Medicine at Juntendo University. He holds an M.D. from Yamanashi Medical College and a Ph.D. from Juntendo University. His research focuses on lung cancer and thymic epithelial tumors, with expertise in chemotherapy, cancer biomarkers, and tissue biopsy. With 139 publications and 3,630 citations, Dr. Shukuya has made significant contributions to the field. He is an active member of the Japanese Respiratory Society, the Japan Lung Cancer Society, the Japanese Society of Medical Oncology, International Society for the Study of Lung Cancer, American Society of Clinical Oncology, and serves as an editor for BMC Cancer. His work continues to advance oncology, improving clinical practices and cancer research.