The previously reported SANET-ep trial (clinicaltrials.gov identifier NCT02588170) demonstrated that surufatinib significantly improves progression-free survival (“PFS”) in patients with advanced extrapancreatic (non-pancreatic) neuroendocrine tumors compared to placebo, with a median PFS of 9.2 months versus 3.8 months, respectively (hazard ratio = 0.334, 95% CI 0.223 to 0.499, p<0.0001). This presented analysis evaluated the safety profile and adverse events of special interest (“AESI”) of surufatinib from SANET-ep data. 93.8% of patients in the surufatinib group and 73.5% of patients in the placebo group had at least one treatment-emergent AESI.
The analysis concluded that AESIs of Grade 3 or higher hypertension and proteinuria occurred more frequently with surufatinib than with placebo, with the most common (at least 3% of patients) grade 3 or greater AESIs being hypertension (40.3% with surufatinib vs. 16.2% with placebo), proteinuria (23.3% vs. 0) and hemorrhage (3.1% vs. 2.9%). It also concluded that AESIs leading to treatment discontinuation were uncommon, with AESIs leading to dose discontinuation in at least 1% of patients being proteinuria (3.9% with surufatinib vs. 0 with placebo), hemorrhage (1.6% vs 1.5%), and hepatic failure (0.8% vs 1.5%). Surufatinib has a manageable safety profile in patients with advanced extra-pancreatic neuroendocrine tumors.
Title: Safety Profile and Adverse Events of Special Interest for Surufatinib in Chinese Patients with Advanced Extra-Pancreatic Neuroendocrine Tumors: Analysis of the Phase 3 SANET-ep Trial
Authors: Jie Li, Jianming Xu, Zhiwei Zhou, Chunmei Bai, Yihebali Chi, Zhiping Li, Nong Xu, Enxiao Li, Tianshu Liu, Yuxian Bai, Sha Guan, Lin Shen
Introduction The previously reported SANET-ep trial (NCT02588170) demonstrated surufatinib significantly improves progression-free survival (PFS) in patients (pts) with advanced extrapancreatic neuroendocrine tumors (epNETs) compared to placebo; median PFS (9.2 vs. 3.8 months; HR = 0.334, 95% CI 0.223 to 0.499, p<0.0001).
Aims The present analysis evaluates the safety profile and adverse events of special interest (AESIs) of surufatinib from SANET-ep data.
Patients and Methods Pts were randomized (2:1) to receive surufatinib (300 mg once daily continuously) or placebo. Treatment-related AESIs and time-to-first occurrence of AESIs were summarized. Predefined AESIs included hepatic failure (HF), proteinuria (P), hypertension (HTN), haemorrhage (H), and acute renal failure (ARF), which were searched with narrow MedDRA Standardized MedDRA Query (SMQ).
Results A total of 121/129 (93.8%) pts in the surufatinib group and 50/68 (73.5%) in the placebo group had ≥ 1 treatment-emergent AESI; the mean relative dose intensity was 86.42% and 96.78%, respectively. The most commonly reported (>10% of pts) AESIs were P (84.5% vs 57.4%), HTN (68.2% vs 30.9%), and H (55.8% vs 27.9%). The most common (≥3% of pts) grade ≥3 AESIs were HTN (40.3% vs 16.2%), P (23.3% vs 0) and H (3.1% vs 2.9%); the median time-to-onset of these events in the surufatinib group was 13.5, 28, and 32 days, respectively. AESIs (≥1% of pts) leading to dose discontinuation were P (3.9% vs 0), H (1.6% vs 1.5%), and HF (0.8% vs 1.5%).
Conclusions The AESIs of Grade ≥ 3 HTN and P occurred more frequently with surufatinib; however, AESIs leading to treatment discontinuation were uncommon. Surufatinib has a manageable safety profile in pts with advanced epNETs.
Keywords extra-pancreatic, neuroendocrine tumors, safety