Advanced sarcoma remains one of oncology’s most difficult treatment challenges, particularly after tumors stop responding to standard chemotherapy, targeted drugs, or immunotherapy. A new multicenter phase 2 study from China reports that surufatinib, an oral drug designed to block several biological pathways involved in tumor growth, produced disease control in most patients whose cancers had progressed after previous treatment. The investigators describe the findings as preliminary but encouraging, especially for people receiving the drug as a second-line treatment and for those with non-uterine leiomyosarcoma, a major subtype of soft-tissue sarcoma.
The trial enrolled 47 adults with unresectable or metastatic sarcoma, meaning their tumors could not be removed completely by surgery or had spread to distant organs. All participants had already received at least one prior treatment and were given surufatinib at a dose of 300 milligrams once daily. Nearly half, 46.8 percent, had undergone two or more previous lines of therapy, placing many of them in a population with few established options. The researchers assessed tumor changes using standard imaging criteria and followed patients for a median of 27.5 months, with the main analysis conducted on September 30, 2025.
The study’s primary endpoint was the 12-week progression-free rate, which measures the proportion of patients whose disease has not worsened three months after treatment begins. Among 45 evaluable patients, 71.1 percent remained progression-free at 12 weeks. This result suggests that surufatinib was capable of slowing tumor growth for a meaningful period in a substantial proportion of participants, even though tumor shrinkage was uncommon. The objective response rate, defined as the percentage of patients whose tumors achieved a confirmed partial or complete reduction, was 11.1 percent. One patient with angiosarcoma experienced a complete response, in which detectable disease disappeared on imaging.
A much larger proportion of patients achieved disease control, reported at 86.7 percent. Disease control includes complete responses, partial responses, and stable disease, in which tumors neither shrink enough to qualify as a response nor grow enough to represent progression. In advanced sarcoma, maintaining stability can be clinically important because even a temporary halt in growth may delay symptoms, preserve organ function, and provide time before another treatment is needed. However, disease control rates should not be interpreted as equivalent to tumor eradication, particularly in a small, single-arm study without a control group for comparison.
Surufatinib’s rationale rests on its ability to interfere with three receptor systems that help tumors grow and survive. The drug inhibits vascular endothelial growth factor receptors, or VEGFRs, which regulate the formation of new blood vessels. Tumors often stimulate blood-vessel growth to secure oxygen and nutrients, a process known as angiogenesis. Surufatinib also blocks fibroblast growth factor receptors, or FGFRs, which participate in cell proliferation, tissue repair, and resistance to anti-angiogenic treatment. Its third target is colony-stimulating factor-1 receptor, or CSF-1R, a signaling protein involved in the development and activity of macrophages, immune cells that can be recruited into tumors and influence their growth, inflammation, and response to therapy.
This three-part mechanism distinguishes surufatinib from drugs that primarily suppress VEGF signaling alone. Blocking VEGFR can deprive tumors of blood supply, but cancers may activate alternative pathways, including FGF signaling, to restore vascular support. At the same time, tumor-associated macrophages can contribute to an immunosuppressive microenvironment and promote tissue remodeling and angiogenesis. By inhibiting CSF-1R in addition to VEGFR and FGFR, surufatinib is intended to affect both the tumor’s vascular support system and elements of the surrounding microenvironment. The clinical data do not yet prove that this combined mechanism caused the observed benefit, but the biological strategy provides a basis for further investigation.
The median progression-free survival for the study population was 4.3 months. Treatment timing appeared to matter considerably: patients who received surufatinib as second-line therapy had a median progression-free survival of 5.7 months, compared with 2.8 months among those treated in later lines. The difference was statistically significant, with a reported p-value below 0.001. Patients with non-uterine leiomyosarcoma also had longer progression-free survival than the broader comparison group, with medians of 7.2 and 4.2 months, respectively. These subgroup findings are potentially important because leiomyosarcoma is biologically diverse, but they must be interpreted cautiously because the trial was small and was not designed as a randomized comparison between sarcoma subtypes or treatment lines.
Prior treatment with an anti-angiogenic drug did not appear to reduce surufatinib’s activity. Median progression-free survival was 3.3 months in patients previously exposed to anti-angiogenic therapy and 4.3 months in those without such exposure, a difference that was not statistically significant. This observation raises the possibility that simultaneous inhibition of VEGFR, FGFR, and CSF-1R could retain activity after resistance to an earlier vascular-targeting treatment. Nevertheless, the result cannot establish that surufatinib overcomes anti-angiogenic resistance, because the analysis was observational and involved limited numbers of patients. A randomized trial would be needed to determine whether its multi-target profile offers a genuine advantage over existing therapies.
Overall survival data were relatively favorable for this early study, although the median had not been reached by the time of analysis. The estimated one-year overall survival rate was 82.2 percent, falling to 63.9 percent at two years. Treatment-related adverse events of grade 3 or higher occurred in 29.8 percent of participants, indicating that serious toxicities were experienced by roughly one in three patients. The abstract describes the safety profile as manageable, but detailed interpretation requires consideration of the specific side effects, dose interruptions, and discontinuations reported in the full study. Because surufatinib affects blood-vessel signaling, clinicians would typically monitor patients for toxicities associated with this drug class, including hypertension, bleeding risk, protein loss in the urine, fatigue, and gastrointestinal effects.
The investigators emphasize that the findings support continued clinical development rather than immediate adoption as a new standard of care. The study was multicenter but single-arm, meaning every participant received surufatinib and there was no control group receiving another therapy or supportive care. Such designs can show whether a treatment has a signal of activity, but they cannot reliably separate drug effects from patient selection, differences in tumor biology, subsequent therapies, or other factors. The sample size was also modest, and sarcoma includes many histological subtypes with distinct molecular features and natural histories. Larger randomized studies, ideally incorporating molecular profiling and carefully defined sarcoma subgroups, will be necessary to establish which patients are most likely to benefit and whether surufatinib can improve survival compared with current treatment choices. For now, the phase 2 results identify a potentially useful multi-pathway approach for advanced sarcoma and suggest that the greatest opportunity may lie in earlier treatment after standard therapy failure, before extensive resistance has developed.
Subject of Research: Surufatinib as second-line or later treatment for advanced sarcoma
Article Title: Efficacy and safety of surufatinib, a novel dual-mechanism inhibitor, as a second-line or further treatment in advanced sarcoma: a multicenter, single-arm, phase 2 trial
Article References: Xu B, Pan Q, Li S, et al. BMC Medicine. 2026.
Image Credits: AI Generated
DOI: 10.1186/s12916-026-05154-7
Keywords: Surufatinib; advanced sarcoma; CSF-1R; non-uterine leiomyosarcoma; phase 2 clinical trial
Tags: advanced sarcoma treatmentdisease control in metastatic sarcomalong-term follow-up in sarcoma trialsmulti-center sarcoma researchnon-uterine leiomyosarcoma therapynovel treatments for refractory sarcomaoral kinase inhibitor in oncologyprogression-free survival in sarcomasafety profile of surufatinibsecond-line sarcoma treatmentsurufatinib phase 2 trialtargeted therapy for soft-tissue sarcoma
