FDA Does Not Approve TKI Surufatinib for Neuroendocrine Tumors

M. Alexander Otto, MMS, PA

May 02, 2022

Chinese manufacturer Hutchmed International announced today that the US Food and Drug Administration (FDA) will not approve surufatinib for the treatment of advanced pancreatic and extrapancreatic neuroendocrine tumors (NETs).

In a complete response letter to the drug company, the FDA stated that the current data on the oral tyrosine kinase inhibitor (TKI) surufatinib — which include data from two phase 3 trials conducted in China and a phase 1 trial conducted in the US — do not support the drug's approval at this time in the US.

According to Hutchmed, the complete response letter indicated that a multiregional clinical trial is required for US approval.

"Although this decision from the FDA is disappointing, we remain confident about the clinical value of surufatinib for NET patients and committed to making surufatinib available to patients globally," Weiguo Su, PhD, chief executive officer and chief scientific officer of Hutchmed, commented in a company press release. "There are very few treatments approved and used in these rare diseases, and patients and physicians would benefit from more options to address the unmet medical need."

Surufatinib has already been approved in China on the basis of data from two phase 3 trials, both published in The Lancet Oncology in late 2020. The drug was first approved in December 2020 for the treatment of advanced extrapancreatic NETs on the basis of the SANET-EP trial. The trial randomly assigned 198 Chinese patients with extrapancreatic NETs in a 2:1 ratio to receive either 300 mg/d or matched placebo. The median progression-free survival (PFS) was 9.2 months in the surufatinib arm, vs 3.8 months with placebo.

The drug was then approved in June 2021 for patients with advanced and progressive pancreatic NETs on the basis of the SANET-P trial. In this trial, 172 patients with pancreatic NETs were randomly assigned to receive surufatinib 300 mg or placebo. Median PFS was 10.9 months with surufatinib, vs 3.7 months with placebo.

In both phase 3 trials, the most common severe treatment-related adverse events were hypertension and proteinuria.

Hutchmed also funded a phase 1 trial in the US that involved 32 heavily pretreated patients with advanced pancreatic and extrapancreatic NETs. In the trial, among those with extrapancreatic NETs, the median PFS was 11.5 months, and the overall response rate (ORR) was 6.3%. Among those with pancreatic NETs, the median PFS was 15.2 months, and the ORR was 18.8%.

In an editorial accompanying the publication of the Chinese trials in The Lancet Oncology, Pamela Kunz, MD, a gastrointestinal medical oncologist at Yale University, said surufatinib yields "a meaningful progression-free survival benefit and response rate in heavily pretreated patients with NETs." In addition, Kunz noted that the trial involving patients with extrapancreatic NETs is the first positive phase 3 study of a TKI for this indication.

However, she cautioned, "We do not yet know how surufatinib will fit into the complex treatment algorithm for NETs. Evidence regarding sequence of therapies is a crucial need in the field."

Approved options on the US market for treating advanced NETs include the generic TKI sunitinib, everolimus, lanreotide, and ¹⁷⁷Lu-dotatate.

Kunz has disclosed no relevant financial relationships.

M. Alexander Otto is a physician assistant with a master's degree in medical science. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape and is an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com.

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