First-line treatment with surufatinib combined with serplulimab and etoposide/cisplatin (EP) regimen exhibits antitumour activity with manageable safety in patients with advanced or metastatic extrapulmonary neuroendocrine carcinoma (NEC), reports a study presented at ESMO Congress 2026.
“The quadruplet regimen of surufatinib plus EP plus serplulimab demonstrated promising antitumour activity as first-line treatment for extrapulmonary NEC, with a confirmed objective response rate (ORR) of 69.8 percent and disease control rate (DCR) of 95.3 percent,” said lead study author and presenter Dr Zhenyu Lin from the Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Lin and his team included 43 systemic treatment-naïve patients (median age 59 years, 65.1 percent male, 65.1 percent had liver metastases) with advanced or metastatic extrapulmonary NEC in this ongoing trial. Eligible participants received surufatinib (250 mg) plus EP regimen (etoposide 100 mg/m2, cisplatin 25 mg/m2), and serplulimab (300 mg) for six cycles, followed by surufatinib plus serplulimab maintenance.
Progression-free survival (PFS) was the primary endpoint, while ORR, DCR, overall survival, and safety were secondary endpoints.
The median Ki-67 index among patients was 70 percent, with 79.1 percent having Ki-67 ≥55 percent. The quadruplet regimen resulted in a median PFS of 9.4 months (95 percent confidence interval, 6.5‒13.9). One patient achieved significant tumour response after 3.6 months of treatment, which allowed for a successful R0 resection. [ESMO 2026, abstract 2394RO]
Of the patients, 69.8 percent had objective response to the combined therapy, and 95.3 percent achieved disease control. Those who achieved complete or partial response demonstrated a significantly longer PFS than nonresponders (11.5 months vs 6.6 months; p=0.0041).
“The median PFS of 9.4 months is encouraging, particularly in a high-risk population with 67.4 percent liver metastases and a median Ki-67 of 70 percent,” Lin said. “Patients achieving objective response derived a meaningful PFS benefit.”
Safety profile
The combination treatment also had an acceptable safety profile. The most common treatment-emergent adverse event (TEAEs) was anaemia (62.8 percent), followed by hypertriglyceridaemia (32.6 percent), nausea (32.6 percent), and neutropenia (30.2 percent). Grade ≥3 TEAEs included anaemia (8.7 percent), decreased neutrophil count (8.7 percent), decreased leukocyte count (6.5 percent), increased bilirubin (4.3 percent), and decreased platelet count (4.3 percent).
Of the patients, 12 in the treatment-status analysis remained on therapy at cutoff, while 31 had ceased treatment. Disease progression (n=16) was the main reason for discontinuation, followed by AEs (n=6), loss to follow-up (n=3), investigator judgment (n=3), surgery (n=2), and withdrawal of consent (n=1).
“The safety profile was manageable and consistent with the expected toxicities of the individual components, with no new safety signals identified,” Lin said. “Grade ≥3 AEs were predominantly haematologic and attributable to the chemotherapy backbone.”
Enrolment for this trial is ongoing, and mature survival data are expected, according to Lin.
“Further exploratory analyses and long-term survival follow-up are warranted to better characterize the benefit of this quadruplet strategy in extrapulmonary NEC,” Lin said.
“Compared with neuroendocrine tumours, NECs are far more aggressive, characterized by poor differentiation, early metastasis, and diagnostic delay, leading to a dismal prognosis,” he said.