New Treatment for Advanced Thymic Carcinoma Shows Promise in Clinical Trial

New Treatment Option for Advanced Thymic Carcinoma Shows Promise: The MARBLE Study

Thymic carcinoma, a rare and aggressive malignancy originating in the thymus gland, is one of the most challenging cancers to treat. It is part of a broader category of thymic epithelial tumors that also includes thymoma, but unlike thymoma, thymic carcinoma is marked by a high degree of invasiveness, metastatic potential, and poor prognosis. Its incidence is extremely low, at just 0.15 cases per 100,000 person-years, making it a rare and often under-researched disease. Despite this, a new treatment combination has shown significant promise in a recent clinical trial, offering hope for improved outcomes in patients with advanced thymic carcinoma.

The Challenge of Treating Advanced Thymic Carcinoma

Thymic carcinoma is notoriously difficult to treat due to its aggressive nature and the lack of targeted therapies. The standard of care for advanced or metastatic thymic carcinoma remains platinum-based chemotherapy, which typically includes drugs such as cisplatin or carboplatin combined with paclitaxel. However, while chemotherapy can offer temporary benefits, its efficacy is often limited, with many patients experiencing disease progression after treatment. Immune checkpoint inhibitors like atezolizumab (an anti-PD-L1 monoclonal antibody) have emerged as a promising therapeutic strategy, particularly in patients who have already been treated with chemotherapy. However, durable responses and effective treatments for chemotherapy-naïve patients have remained an unmet clinical need.

In an effort to address this critical gap, a groundbreaking study, known as the MARBLE study, has investigated a potential new treatment option that combines atezolizumab, carboplatin, and paclitaxel. This combination aims to harness the benefits of both chemotherapy and immunotherapy in treating advanced or recurrent thymic carcinoma.

The MARBLE Study: A Multicenter Clinical Trial

The MARBLE study, conducted across 15 hospitals in Japan, was a multicenter, single-arm, phase II clinical trial designed to assess the effectiveness of the combination of atezolizumab with carboplatin and paclitaxel in patients with advanced or recurrent thymic carcinoma. Led by Associate Professor Takehito Shukuya and his team from the Department of Respiratory Medicine at Juntendo University, Japan, this trial enrolled 48 patients with histologically confirmed thymic carcinoma.

The trial was divided into two phases. In the induction phase, patients received the combination of atezolizumab, carboplatin, and paclitaxel every three weeks for up to six cycles. Following this, patients who had non-progressive disease moved on to the maintenance phase, during which they received atezolizumab alone every three weeks for up to two years.

The goal was to evaluate not only the efficacy of the treatment but also its safety profile and identify any potential predictive biomarkers for treatment response. The findings of the study were published in the March 2025 issue of The Lancet Oncology, offering a new and exciting potential treatment option for this rare and aggressive cancer.

Promising Results and Efficacy

The results from the MARBLE study were encouraging. With a median follow-up of 15.3 months, the combination of atezolizumab, carboplatin, and paclitaxel achieved an objective response rate (ORR) of 56%. This result significantly outperformed historical outcomes from chemotherapy alone, where the ORR is often much lower.

Additionally, the study found a median progression-free survival (PFS) of 9.6 months, another improvement over standard chemotherapy. With a disease control rate (DCR) of 98%, the results were even more impressive. Of the 48 patients enrolled, 56% achieved partial responses, while 42% maintained stable disease.

These results are particularly notable in a disease as aggressive and difficult to treat as thymic carcinoma, offering hope for patients who have traditionally had limited treatment options.

Safety Profile and Tolerability

As expected, the combination therapy had a safety profile consistent with the known effects of atezolizumab, carboplatin, and paclitaxel. There were no new safety concerns or treatment-related deaths. However, patients did experience adverse events, the most common of which were neutropenia, leukopenia, maculopapular rash, and febrile neutropenia. These side effects were manageable and consistent with what has been observed in other cancer therapies involving these agents.

Importantly, the study also found that patients with higher programmed cell death ligand 1 (PD-L1) expression on tumor or immune cells had longer progression-free survival, highlighting the potential of PD-L1 expression as a predictive biomarker for treatment response. This finding could guide future personalized treatment strategies, improving outcomes for thymic carcinoma patients by selecting those most likely to benefit from this combination therapy.

The Future of Thymic Carcinoma Treatment

Dr. Shukuya and his team have expressed optimism about the future of this treatment combination, suggesting that it could become the new standard of care for patients with advanced thymic carcinoma. He commented, “The combination regimen delivered durable tumor responses and prolonged disease control with manageable safety, positioning it as a potential new standard of care.” With these promising results, there is anticipation that insurance coverage for the treatment could be approved in Japan and globally in the near future.

The MARBLE study represents a significant step forward in the treatment of thymic carcinoma, offering hope for patients who have long had few options. By combining the benefits of chemotherapy and immunotherapy, the study addresses the existing therapeutic gap for this rare cancer and may pave the way for more effective and durable treatments in the future.

Conclusion

The MARBLE study provides exciting evidence that a combination of atezolizumab, carboplatin, and paclitaxel could be an effective treatment option for advanced thymic carcinoma. The results indicate that this regimen not only improves progression-free survival but also offers durable tumor responses with manageable safety concerns. These findings could represent a new standard of care, providing a much-needed treatment option for patients suffering from this rare and aggressive cancer.

As research in this area progresses, the hope is that more targeted therapies and biomarker-driven treatments will continue to emerge, improving outcomes and long-term survival rates for patients with thymic carcinoma.

Learn more: https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00001-4/abstract