Surufatinib improves PFS in patients with advanced pNETs
Surufatinib, a novel small-molecule inhibitor that targets tumour angiogenesis and immune evasion, improves progression-free survival (PFS) in patients with progressive, advanced, well-differentiated pancreatic neuroendocrine tumours (pNETs), according to results of the SANET-p trial presented at the European Society for Medical Oncology (ESMO) Virtual Congress 2020.
In the phase III trial conducted in 21 hospitals in China, adult patients with grade 1/2, locally advanced or metastatic, well-differentiated pNETs that progressed on ≤2 previous systemic regimens were randomized (2:1) to receive surufatinib (300 mg QD orally in 4-week treatment cycles) (n=113; median age, 51 years; male, 53 percent) or placebo (n=59; median age, 48 years; male, 47 percent). Patients with functional NETs that required treatment with long-acting somatostatin analogues and those with disease progression on prior treatment with VEGF or VEGF receptor inhibitors were excluded. [Xu J, et al, ESMO 2020, abstract 1156O; Lancet Oncol 2020, doi: 10.1016/S1470-2045(20)30493-9]
“The trial’s primary endpoint was met. After a median follow-up of 19.3 months in the surufatinib arm and 11.1 months in the placebo arm, median investigator-assessed PFS was 10.9 months for patients receiving surufatinib vs 3.7 months for those receiving placebo, with a hazard ratio [HR] of 0.49 [95 percent confidence interval (CI), 0.319 to 0.755],” reported investigator Dr Jianming Xu of the Chinese PLA General Hospital, Beijing, China. “The PFS benefit of surufatinib was consistent across major subgroups.”
PFS assessed by a blinded independent image review committee (BIIRC) was also significantly improved with surufatinib vs placebo (median, 13.9 months vs 4.6 months; HR, 0.339; 95 percent CI, 0.209 to 0.549; p<0.0001).
“The trial met the early stopping criteria based on PFS superiority with surufatinib vs placebo observed at the pre-planned interim analysis, and was terminated early on recommendation by the independent data monitoring committee,” said Xu.
Objective response rate (ORR) was likewise significantly improved with surufatinib vs placebo (19.2 percent vs 1.9 percent; p=0.0021), with all responders having partial responses. At the interim analysis, tumour shrinkage of >10 percent was observed in 68 percent vs 15 percent of patients treated with surufatinib vs placebo.
“Overall survival data were not yet mature, with follow-up ongoing,” said Xu.
In the trial, median treatment duration was 229 days in the surufatinib arm vs 123 days in the placebo arm. The mean relative dose intensity was 89 percent vs 97.6 percent.
“Most treatment-emergent adverse events [TEAEs] were manageable with dose interruption and modification,” noted Xu. “Grade ≥3 TEAEs were reported in 69.9 percent of patients in the surufatinib arm vs 27.1 percent of those in the placebo arm, while serious AEs were reported in 26.7 percent vs 8.5 percent of the patients.”
The most common grade ≥3 TEAEs were hypertension (38 percent with surufatinib vs 7 percent with placebo), proteinuria (10 percent vs 2 percent), and hypertriglyceridaemia (7 percent vs 0 percent).
TEAEs led to dose interruption, reduction or discontinuation in 45.1 percent vs 23.7 percent, 38.9 percent vs 5.1 percent, and 10.6 percent vs 6.8 percent of the patients, respectively.
“The significant and clinically meaningful improvement in PFS, together with tolerable safety profile, support surufatinib as a treatment option for patients with progressive, advanced well-differentiated pNETs,” Xu concluded.