Thymic Cancer Treatments Highlighted by Professor Wentao Fang at ESMO Asia 2024

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“ESMO Asia 2024, Wentao Fang Discusses Advances in Thymic Cancer Treatments.

The 2024 European Society for Medical Oncology Asia Congress (ESMO Asia 2024) was held in Singapore from December 6 to 8.

In the session featuring selected oral presentations on thoracic oncology, Wentao Fang from Shanghai East Hospital, Tongji University presented findings from the AL3810-202 trial (Abstract 625O), which evaluated Lucitanib (Delitinib, AL3810) as a second-line or subsequent therapy for advanced recurrent or metastatic thymic carcinoma.

During the conference, Oncology Frontier invited Professor Fang to discuss the study findings and share highlights from the event.

Thymic Cancer in China: Incidence and Challenges

Q: Thymic cancer is a rare thoracic malignancy. Can you share its incidence in China and the current treatment challenges for advanced thymic cancer?

Professor Fang: Thymic carcinoma is a highly malignant subtype of thymic tumors, accounting for approximately 15% of cases. Thymic tumors are rare to begin with, and thymic carcinoma is even rarer. At the time of initial diagnosis, a significant proportion of thymic carcinoma patients are in advanced stages. While radical surgical resection can achieve good outcomes for some, the risk of postoperative recurrence and metastasis remains high. For patients with metastatic disease, effective systemic therapies are needed.

Chemotherapy is the standard first-line systemic treatment recommended by both domestic and international guidelines. However, its efficacy is limited, with real-world response rates ranging from 20% to 40%. For patients who fail first-line chemotherapy, there are few treatment options, highlighting an urgent need for more effective therapies.

Lucitanib (AL3810) in Advanced Thymic Carcinoma

Q: Based on the 2024 ESMO Asia findings, how do the efficacy and safety of Lucitanib (AL3810) fare for advanced recurrent or metastatic thymic carcinoma?

Professor Fang: For patients with advanced thymic carcinoma who have failed first-line chemotherapy, we explored new treatment options. Lucitanib is a multi-targeted anti-angiogenic agent that demonstrated promising efficacy in an initial Phase I trial (n=12), with a median progression-free survival (mPFS) of 32 weeks. This encouraged us to conduct the Phase II AL3810-202 trial.

This randomized controlled trial is the largest global study to date for thymic carcinoma (n=68) and the only one with a randomized design. At ESMO Asia 2024, we reported the results:

Investigator-assessed mPFS: 6.6 months in the Lucitanib group vs. 1.9 months in the placebo group (P=0.0306, HR=0.53), achieving statistical significance.
Independent Review Committee (IRC)-assessed mPFS: 5.8 months for Lucitanib vs. 3.7 months for placebo (P=0.1050, HR=0.60).

Statistical analyses, including weighted log-rank tests, restricted mean survival time analysis, and Bayesian analysis, consistently demonstrated significant advantages for Lucitanib. Overall, the efficacy data for Lucitanib are highly promising.

In terms of safety, the most common Grade 3 treatment-related adverse events (TRAEs, ≥5%) in the Lucitanib group were hypertension, proteinuria, and thrombocytopenia—common toxicities for this drug class. Importantly, no Grade 4 or 5 TRAEs were observed. Other typical toxicities of anti-angiogenic drugs, such as hand-foot syndrome and oral mucositis, occurred in less than 5% of patients. Thus, Lucitanib demonstrates manageable safety.

In summary, for advanced thymic carcinoma patients who have failed chemotherapy, Lucitanib offers an effective and promising treatment option where limited alternatives exist.

Immunotherapy in Thymic Carcinoma

Q: Immunotherapy and combination regimens have shown success in advanced lung cancer. Do you see similar potential in thymic carcinoma?

Professor Fang: First- and second-line treatment options for thymic carcinoma are limited and often unsatisfactory, which has prompted research into immunotherapy. Small Phase II single-arm trials have shown the potential of immunotherapy in second-line and later settings for thymic carcinoma. Based on these findings, PD-1 inhibitor pembrolizumab is now guideline-recommended for second-line treatment.

Building on this success, researchers are investigating immunotherapy in earlier lines of treatment. Studies are underway to assess the efficacy of immunotherapy alone, immunotherapy combined with chemotherapy, or immunotherapy with anti-angiogenic agents in first-line settings.

Our team is also exploring first-line chemoimmunotherapy for advanced thymic carcinoma, including clinical trials of neoadjuvant immunotherapy plus chemotherapy to evaluate the feasibility of surgery for unresectable cases.

At ESMO Asia 2024,  Tomoyasu Mimori from Japan presented Phase II trial results of atezolizumab combined with chemotherapy for first-line treatment of thymic tumors, reporting an objective response rate (ORR) of 56.3%. I believe first-line immunotherapy for thymic carcinoma holds significant potential for further exploration.

Reflections on ESMO Asia 2024

Q: What were your key takeaways from the 2024 ESMO Asia Congress, and which thoracic oncology studies interested you the most?

Professor Fang: I attended the selected oral presentations on thoracic oncology, which focused on thymic tumors and non-small cell lung cancer (NSCLC). Both Professor Tomoyasu Mimori and I presented findings on anti-angiogenic therapy and chemoimmunotherapy for thymic tumors, sparking discussions among experts about conducting clinical trials for rare diseases like thymic carcinoma.

Designing clinical trials for rare diseases is exceptionally challenging. Apart from the Lucitanib trial, most studies have been small, non-randomized, and statistically underpowered, leading to evidence of limited strength. Traditional statistical methods are often inadequate for such rare diseases. Leveraging real-world data and prior clinical research in trial design can enhance statistical power, validate the benefits of innovative drugs, and improve treatment paradigms for rare diseases like thymic carcinoma.

In lung cancer, notable presentations included:

Beamion LUNG-1 study (Japan): Zongertinib showed high response rates and manageable safety in HER2-mutant advanced/metastatic NSCLC.
PACIFIC-5 study (China): Professor Yi-Long Wu reported positive PFS results.
TROPION-Lung01 & TROPION-Lung05 studies (Korea):  Myung-Ju Ahn highlighted the encouraging efficacy and safety of Dato-DXd in EGFR-mutant NSCLC.

Personally, I am most intrigued by the diminishing boundaries between surgery, radiotherapy, and systemic therapy as more effective targeted and immunotherapies emerge. Precision treatment strategies increasingly depend on molecular biomarkers rather than traditional standards like tumor stage or histological type. This shift underscores the need for ongoing exploration in the era of personalized medicine.

Professor Wentao Fang

Affiliation: Director of Thoracic Surgery, Shanghai East Hospital, Tongji University

Titles: Professor, Doctoral Supervisor

Roles: Honorary Director, Mediastinal Tumor Committee, Chinese Anti-Cancer Association Deputy Chair, Esophageal Cancer Committee, Chinese Anti-Cancer Association Deputy Chair, Lung Tumor Committee, Chinese Medical Education Association Deputy Director, Thoracic Surgery Quality Control Center, National Health Commission Standing Member, Thoracic Surgery Branch, Chinese Medical Doctor Association Member, Shanghai Surgical Society.”