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
Authors
Takehito Shukuya1, Tetsuhiko Asao1, Yasushi Goto2, Tomoyasu Mimori1, Koichi Takayama3, Kyoichi Kaira4, Hiroshi Tanaka5, Ryo Ko6, Yoshihiro Amano7, Motoko Tachihara8, Takuji Suzuki9, Junko Tanizaki10, Shunichi Sugawara11, Yoshitaka Zenke12, Yukina Shirai1, Takuo Hayashi13, Keita Mori14, Kazuhisa Takahashi1
Title of original paper
Activity and safety of atezolizumab plus carboplatin and paclitaxel in patients with advanced or recurrent thymic carcinoma (MARBLE): a multicentre, single-arm, phase 2 trial
Journal
The Lancet Oncology
DOI
10.1016/S1470-2045(25)00001-4
Affiliations
1Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Japan
2Department of Thoracic Oncology, National Cancer Center Hospital, Japan
3Department of Pulmonary Medicine, Kyoto Prefectural University of Medicine, Japan
4Department of Respiratory Medicine, International Medical Center, Saitama Medical University, Japan
5Department of Internal Medicine, Niigata Cancer Center Hospital, Japan
6Division of Thoracic Oncology, Shizuoka Cancer Center, Japan
7Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine, Japan
8Division of Respiratory Medicine, Kobe University Graduate School of Medicine, Japan
9Department of Respirology, Chiba University, Japan
10Department of Medical Oncology, Kindai University Faculty of Medicine, Japan
11Department of Pulmonary Medicine, Sendai Kousei Hospital, Japan
12National Cancer Center Hospital East, Japan
13Department of Human Pathology, Juntendo University Graduate School of Medicine, Japan
14Department of Biostatistics, Clinical Research Center, Shizuoka Cancer Center, Japan
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.
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