Editor's Note: The 2024 European Society for Medical Oncology (ESMO) Annual Meeting recently concluded in Barcelona, Spain, bringing together the world's leading oncology experts. At this year's conference, Dr. Yuhong Zhou from Zhongshan Hospital, Fudan University, presented a phase II multicenter clinical trial that explored the efficacy and safety of surufatinib combined with gemcitabine in soft tissue sarcoma (STS) patients who had failed anthracycline chemotherapy or anlotinib monotherapy. The study offers new perspectives for clinical practice.

Soft tissue sarcoma (STS) is a group of mesenchymal-origin malignant tumors, accounting for about 0.72% to 1.05% of all solid tumors. According to the World Health Organization (WHO), there are over 50 histological subtypes of STS. For early-stage STS, radical surgery remains the primary treatment. However, for unresectable or metastatic advanced STS, palliative chemotherapy based on ifosfamide and anthracyclines remains the first-line treatment, with a median overall survival (OS) of around 12 to 18 months.

In recent years, advances in understanding the mechanisms of STS have led to new treatment strategies. Targeted therapies, such as small-molecule anti-angiogenic drugs and specific signal transduction inhibitors, have begun to emerge, offering new hope for STS patients. Previous studies have shown that surufatinib, a multi-target small molecule anti-angiogenic drug, can inhibit tumor angiogenesis, and its combination with chemotherapy can produce synergistic effects.

Study Overview

Surufatinib combined with gemcitabine in soft tissue sarcoma (STS) patients failed with anthracyclines chemotherapy or monotherapy post-anlotinib progression: A multi-center, phase II trial(Abstract No. 1740P)

In this study presented at ESMO, surufatinib combined with gemcitabine showed promising efficacy and safety in patients with soft tissue sarcoma (STS) who had progressed after standard chemotherapy or anlotinib monotherapy. Adult STS patients received surufatinib and gemcitabine every three weeks. The primary endpoint of the study was progression-free survival (PFS), with secondary endpoints including disease control rate (DCR), objective response rate (ORR), and overall survival (OS).

As of the data cutoff on July 15, 2024, the objective response rate was approximately 18%, and the disease control rate exceeded 80%. The median PFS was about 4.5 months. Notably, patients with lung metastases experienced a longer PFS, suggesting that this combination therapy may offer greater survival benefits for this subgroup. Additionally, the safety profile of the treatment was consistent with previous studies, with a low incidence of grade 3 or higher adverse events (AEs), indicating that the combination is well tolerated.

Overall, surufatinib combined with gemcitabine has shown potential in the treatment of STS, providing a new option for patients who have failed previous treatments. As the study progresses and molecular analyses are completed, there is hope for more personalized treatment approaches for STS patients.

Dr. Yuhong Zhou: STS encompasses a variety of histological subtypes, such as undifferentiated pleomorphic sarcoma (UPS), liposarcoma (LS), leiomyosarcoma (LMS), synovial sarcoma (SS), angiosarcoma (AS), fibrosarcoma (FS), and malignant peripheral nerve sheath tumor (MPNST). The genetic and clinical characteristics vary significantly among these subtypes, leading to wide differences in survival outcomes.

For unresectable or metastatic advanced STS, the first-line treatment remains palliative chemotherapy based on ifosfamide and anthracyclines. With advances in targeted therapies, molecular anti-angiogenic drugs such as anlotinib have been approved for treating certain subtypes of STS, including alveolar STS, clear cell sarcoma, and other advanced STS that have progressed after anthracycline-based chemotherapy. However, there is still no widely accepted second-line treatment for STS patients who fail first-line therapies, and treatment options are limited, leaving much room for improvement.

For many types of STS, anti-angiogenic tyrosine kinase inhibitors (TKIs) are a second-line or later treatment option. TKIs such as pazopanib, anlotinib, and regorafenib have shown median PFS of 4.6 months, 6.27 months, and 3.7 months, respectively, in second-line treatment. Exploring the combination of anti-angiogenic TKIs with chemotherapy is currently an active area of research in STS treatment.

Anlotinib, approved by the National Medical Products Administration (NMPA) as the only TKI for STS, has become widely used in clinical practice. However, resistance to anlotinib is an inevitable challenge. Persistent inhibition of VEGFR can activate compensatory pathways, such as FGFR, which drive tumor progression.

Surufatinib not only targets VEGFR-1/2/3 but also inhibits FGFR-1 and CSF-1R. Therefore, for patients who develop resistance to anlotinib, surufatinib offers a theoretical advantage in achieving tumor control. The findings presented at this year’s ESMO conference confirm the anti-tumor activity of surufatinib combined with gemcitabine in STS patients who have failed anthracycline chemotherapy, especially in those with lung metastases. Moreover, surufatinib monotherapy has shown initial efficacy in patients who have previously received TKI treatment. We look forward to future studies with larger sample sizes that will provide further evidence and treatment options for STS patients treated with surufatinib.

Dr. Yuhong Zhou

Deputy Director of the Oncology Department, Zhongshan Hospital, Fudan University Standing Member of the Sarcoma Committee, Chinese Society of Clinical Oncology (CSCO) Standing Member of the Sarcoma Committee, Chinese Anti-Cancer Association Chair of the Bone and Soft Tissue Tumor Group, Shanghai Medical Association Oncology Branch Vice Chair of the Sarcoma Committee, Shanghai Anti-Cancer Association