Subgroup Analysis by Ki67 and Primary Tumor Origins of the Phase 3 SANET-ep Study of Surufatinib

Subgroup analysis data of the randomized phase 3 SANET-ep trial indicate that the clinical benefits of the multitargeted tyrosine kinase inhibitor surufatinib therapy also extended to major subgroups by Ki67 and primary tumor origin in patients with advanced, well-differentiated extrapancreatic neuroendocrine tumors (NETs).

The randomized, placebo-controlled phase 3 SANET-ep study (NCT02588170) demonstrated significant prolongation of progression-free survival (PFS) with surufatinib therapy compared with placebo in patients with progressive, well-differentiated, advanced extrapancreatic NETs in the intent-to-treat population.¹ Given that the proliferation marker Ki67 and primary tumor origins are major prognostic factors in NETs, a post-hoc efficacy analysis of the SANET-ep study was conducted and reported at the European Society for Medical Oncology Virtual Congress 2020.

In the post-hoc analysis, the primary end point of investigator-assessed PFS and secondary end point of objective response rate (ORR) were analyzed by Ki67 subcategory (<3%, 3%-10%, and >10%) and primary tumor origins (foregut, midgut, hindgut, others, or unknown) in patients with advanced, well-differentiated (grade 1 or 2) extrapancreatic NETs.

The post-hoc analysis showed that, compared with placebo, median PFS was significantly prolonged with surufatinib therapy in the Ki67 3% to 10% cohort (7.6 vs 4.6 months; hazard ratio [HR], 0.47; P = .0012), Ki67 >10% cohort (8.3 vs 2.1 months; HR, 0.14; P <.0001), foregut cohort (8.4 vs 4.6 months; HR, 0.29; P = .0001), and hindgut cohort (8.3 vs 2.1 months; HR, 0.35; P = .0014). Although numerical PFS improvement with surufatinib in the other subgroups, including Ki67 <3% (13.9 vs 7.4 months; HR, 0.43; P = .0557), midgut (19.2 vs 8.9 months; HR not analyzed because of small sample size), and unknown origin (9.2 vs 5.5 months; HR, 0.56; P = .2943) compared with placebo, these did not reach statistical significance. The ORR achieved with surufatinib therapy in the Ki67 <3% subgroup was 4.8%; in the Ki67 3% to 10% cohort, 7.7%; and in the Ki67 >10%, 20.0%, compared with 0% in the placebo arm. The ORR with surufatinib in the foregut subgroup was 18.4%, in the midgut subgroup it was 16.7%, and in the unknown origin subgroup it was 10.0%; no response was observed in the hindgut or other origins subgroups.

The results of this exploratory analysis indicated that the clinically significant benefits of surufatinib therapy observed in the primary analysis of the SANET-ep trial also extended to major subgroups by Ki67 and primary tumor origin in patients with advanced, well-differentiated extrapancreatic NETs.

Source: Zhou Z, et al. Ann Oncol. 2020;31(4_suppl). Abstract 1165P.

Reference
1. Xu J, et al. Lancet Oncol. 2020;21:1500-1512.