The clinical context is stark. Small cell lung cancer accounts for roughly 15 percent of all lung cancer cases, translating to an estimated 250,000 new cases and 200,000 deaths globally each year. Between 80 and 85 percent of patients already have extensive-stage disease at diagnosis, meaning the cancer has spread beyond one lung and nearby lymph nodes. For more than three decades, platinum-based chemotherapy was the backbone of first-line treatment, producing initial response rates of at least 50 percent but yielding a median overall survival of only 7 to 10 months and a two-year survival rate of just 10 to 20 percent. The arrival of immune checkpoint inhibitors changed the landscape: platinum chemotherapy combined with PD-1 or PD-L1 blockade now raises objective response rates to 60 to 80 percent, extends progression-free survival to 4.5 to 5.8 months, and pushes median overall survival to 10.8 to 15.5 months.

Yet even this improvement has a ceiling. More than half of patients relapse within three months of beginning maintenance immunotherapy, the phase of treatment intended to consolidate the gains made during induction. This persistent vulnerability has driven researchers to explore whether anti-angiogenic agents, which target the blood vessels that feed tumors, could sensitize the tumor microenvironment to immune attack. Tumors secrete pro-angiogenic factors such as vascular endothelial growth factor and fibroblast growth factor, which generate abnormal, dysfunctional vasculature. That malformed vasculature actively suppresses immunity by physically blocking the infiltration of effector T cells and dendritic cells while fostering immunosuppressive cell populations. Anti-angiogenic therapy can normalize these vessels, restoring immune cell traffic and amplifying the effect of checkpoint blockade.

Surufatinib is a particularly interesting candidate in this regard because it does more than starve tumors of their blood supply. In addition to inhibiting VEGF receptors 1, 2, and 3 and FGFR-1, the drug blocks colony-stimulating factor-1 receptor, a pathway that drives macrophage polarization toward the immunosuppressive M2 phenotype. By preventing that polarization and promoting the infiltration of cytotoxic CD8-positive T cells into tumors, surufatinib is designed to work in concert with PD-1 or PD-L1 inhibitors rather than merely alongside them. The drug is already approved in China for unresectable locally advanced or metastatic non-pancreatic neuroendocrine tumors and for advanced pancreatic neuroendocrine tumors, giving clinicians an established safety database to draw upon.

The study enrolled 21 patients at seven centers in China between 19 September 2022 and 30 June 2023. Eligible participants were aged 18 to 75 with histologically or cytologically confirmed extensive-stage small cell lung cancer that had not progressed, per RECIST version 1.1 criteria, after four to six cycles of platinum-based chemotherapy combined with a PD-1 or PD-L1 inhibitor such as toripalimab, sintilimab, serplulimab, or durvalumab. Patients had an Eastern Cooperative Oncology Group performance status of 0 or 1 and adequate organ function. Those with treated, asymptomatic brain metastases could enroll under strict conditions, including a maximum intracranial lesion diameter of 1.0 centimeter and no involvement of the brainstem or spinal cord. Maintenance therapy consisted of oral surufatinib at 250 milligrams once daily plus the same checkpoint inhibitor used during induction, continued until loss of clinical benefit, unacceptable toxicity, or other protocol-defined criteria.

The efficacy results were encouraging. Median progression-free survival measured from the start of maintenance therapy was 4.0 months, with a 95 percent confidence interval of 1.9 to 6.4 months, while progression-free survival from the initiation of induction treatment reached a median of 8.8 months. Median overall survival from maintenance initiation had not been reached after a median follow-up of 17.1 months, and the 18-month overall survival rate stood at 57.1 percent. Among the 13 patients with measurable lesions at baseline, the objective response rate was 23.1 percent, with all responses being partial responses, and the disease control rate was 53.8 percent. Notably, tumor shrinkage was observed in eight of those 13 evaluable patients, or 61.5 percent, and the median duration of response had not been reached at the time of analysis.

Subgroup analyses, though limited by the small sample size, revealed patterns of clinical interest. Patients without liver metastases had numerically better outcomes than those with hepatic involvement: the 18-month progression-free survival rate from induction initiation was 36.4 percent versus 12.7 percent, and the corresponding 18-month overall survival rate was 75.0 percent versus 33.3 percent. Higher body mass index, an Eastern Cooperative Oncology Group score of 0, younger age, cisplatin-based rather than carboplatin-based chemotherapy, and five to six induction cycles were also associated with numerically superior outcomes. These signals align with known prognostic factors in extensive-stage disease and suggest that patient selection could amplify any benefit the combination provides.

Safety data supported the tolerability of the regimen. Nineteen of 21 patients, or 90.5 percent, experienced at least one treatment-related adverse event, but the majority were mild to moderate. Grade 3 or higher events occurred in six patients, or 28.6 percent, most commonly decreased platelet and neutrophil counts. The most frequent treatment-related adverse events overall were diarrhea at 38.1 percent, thrombocytopenia at 28.6 percent, and leukopenia, asthenia, rash, and hypertension at 19.0 percent each. Strikingly, classic anti-angiogenic toxicities such as proteinuria and hand-foot syndrome were not observed at all. Only two patients, 9.5 percent, discontinued treatment because of adverse events, and no treatment-related deaths occurred. Five patients experienced immune-related adverse events, all grade 1 to 2, with a single serious case of grade 2 immune-mediated pneumonitis managed successfully with corticosteroids.

The investigators are careful to frame these results within the study’s limitations. The trial was small, single-arm, and conducted without a formal statistical hypothesis, so the findings require confirmation in larger randomized controlled trials. Because only patients who had not progressed during induction were enrolled, survival figures calculated from the start of induction are subject to guarantee-time bias, an immortal time effect that excludes patients who progressed or died early. The heterogeneity of induction regimens, including different platinum agents, different checkpoint inhibitors, and variable cycle numbers, further complicates attribution of the maintenance benefit specifically to surufatinib, and no biomarker analyses such as PD-L1 expression were performed to identify optimal responders.

Even with those caveats, the results position surufatinib within a rapidly evolving treatment paradigm. The ETER 701 study demonstrated that adding the anti-angiogenic agent anlotinib to first-line immunochemotherapy with benmelstobart extended median overall survival to 19.3 months and progression-free survival to 6.9 months, a regimen approved in China in 2024. Against that benchmark, the 8.8-month progression-free survival observed with surufatinib maintenance, together with a 12-month overall survival rate of 85.7 percent from induction initiation and a grade 3-plus toxicity rate numerically lower than comparable anti-angiogenic combinations, suggests genuine potential. A phase 2b portion of the study is planned to compare surufatinib against placebo plus a PD-1 or PD-L1 inhibitor as first-line maintenance therapy, which will provide the randomized validation needed to determine whether this triple-mechanism approach, attacking tumor vasculature, macrophage-mediated immune suppression, and checkpoint blockade resistance simultaneously, can become a new standard of care for one of oncology’s most stubborn diseases.

Subject of Research: Surufatinib combined with PD-1/PD-L1 inhibitors as first-line maintenance therapy for extensive-stage small cell lung cancer

Article Title: Efficacy and safety of surufatinib plus PD-1/PD-L1 inhibitors as first-line maintenance therapy in extensive-stage small cell lung cancer

Article References: Tao, H., Chen, J., Lv, D., Wang, J., Ma, J., Yi, T., Wu, S., Zhou, X., Zhang, X., Chen, D., Fan, S., Zhong, C., Guan, C., Shi, M., Su, W., & Hu, Y. (2026). Efficacy and safety of surufatinib plus PD-1/PD-L1 inhibitors as first-line maintenance therapy in extensive-stage small cell lung cancer. Holistic Integrative Oncology, 5(1), Article 59. https://doi.org/10.1007/s44178-026-00281-w

Image Credits: AI Generated

DOI: 10.1007/s44178-026-00281-w

Keywords: small cell lung cancer, surufatinib, PD-1 inhibitors, PD-L1 inhibitors, maintenance therapy, anti-angiogenic therapy, immunotherapy, phase 2 trial, CSF-1R, VEGFR, progression-free survival, oncology