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The National Medical Products Administration of China has approved surufatinib for the treatment of patients with advanced pancreatic neuroendocrine tumors.
The National Medical Products Administration of China has approved surufatinib (Sulanda) for the treatment of patients with advanced pancreatic neuroendocrine tumors (pNETs), according to an announcement from HUTCHMED Limited.1
The regulatory decision is supported by data from the phase 3 SANET-p trial (NCT02589821), which showed that surufatinib resulted in a median progression-free survival (PFS) of 10.9 months (95% CI, 7.5-13.8) per investigator assessment vs 3.7 months (95% CI, 2.8-5.6) with placebo (HR, 0.491; 95% CI, 0.391-0.755; P = .0011).2 Notably, the clinical benefit achieved with surufatinib was noted across most of the key patient subsets examined.
“Since its launch in January this year, patients with extra-pancreatic NETs have benefitted from treatment with surufatinib through its unique mod of action by both inhibiting angiogenesis and promoting the body’s immune response against tumor cells," Christian Hogg, chief executive officer of HUTCHMED, stated in a press release. "With today’s approval, we are now able to provide this unique therapy to [patients with] NETs with pancreatic tumor origin, as well.”
Surufatinib is a small molecule kinase inhibitor that targets VEGFRs, FGFR1, and CSF-1R. By simultaneously targeting angiogenesis through VEGFRs/FGFR1 and modulating the tumor immune microenvironment through CSF-1R, the agent offers a potent strategy for strengthening antitumor activity.
The phase 3 trial enrolled patients with well-differentiated pancreatic NETs that was pathological grade 1 or 2. Patients had to have locally advanced disease or distant metastasis, documented radiological disease progression within 1 year, and progression on 2 or fewer kinds of previous systemic therapies for advanced disease. Patients could not have progressed on previous VEGF/VEGFR inhibitors.
A total of 172 patients were randomized 2:1 to receive either surufatinib at a once-daily dose of 300 mg (n = 113) or placebo (n = 59) until disease progression. Once patients on the placebo arm experienced progression, they went on to open-label surufatinib. Stratification factors included prior treatment (treated vs naïve), pathological grade (1 vs 2), and ECOG performance status (0 vs 1).
The primary end point of the trial was investigator-assessed PFS, while secondary end points included objective response rate (ORR), disease control rate (DCR), duration of response (DOR), time to response (TTR), and overall survival (OS), and safety and tolerability.
The median age of study participants was 49.5 years, 50.3% were male, and 68.8% had an ECOG performance status of 0. Additionally, 86.2% of patients had pathological grade 2 disease, 91.8% had non-functional tumors, 93.6% had liver metastasis, and 65.8% had prior systemic therapy for advanced disease. Of those who received prior treatment, 24.8% received chemotherapy, 45% received a somatostatin analogue, and 8.7% received everolimus (Afinitor). About one-quarter of patients had previously received locoregional therapy.
Additional data showed that the PFS per blinded independent image review committee (BIIRC) was consistent with what had been observed per investigator assessment. The median PFS in the investigative and control arms per BIIRC was 13.9 months (95% CI, 11.0-24.9) and 4.6 months (95% CI, 3.6-7.4), respectively (HR, 0.339; 95% CI, 0.209-0.549; P <.0001).
Surufatinib elicited an ORR of 19.2% (95% CI, 12.2%-28.1%) vs 1.9% (95% CI, 0.0%-10.1%) with placebo (P = .0021). Moreover, DCRs in the investigative and control arms were 80.8% (95% CI, 71.9%-87.8%) and 66.0% (95% CI, 51.7%-78.5%), respectively (P = .0774). The TTR with surufatinib was 3.8 months (95% CI, 2.3-7.3) vs 7.4 months with placebo. The median DOR with surufatinib was 7.4 months. The OS data were immature, with only 16.9% of events reported.
Regarding safety, any-grade treatment-emergent adverse effects (TEAEs) were reported in 95.6% of those who received surufatinib vs 91.5% of those given placebo; grade 3 or higher TEAEs were reported in 69.9% vs 27.1% of patients, respectively.
More patients on the investigational arm experienced TEAEs that led to dose interruption, dose reduction, and dose discontinuation than those on the control arm, at 45.1% and 23.7%, respectively, 38.9% vs 5.1%, respectively, and 10.6% vs 6.8%, respectively.
The most common TEAEs that occurred in at least 20% of patients in the investigative and control arms were hypertension (66.4% vs 22.0%, respectively), proteinuria (65.5% vs 54.2%), and diarrhea (51.3% vs 25.4%).
In December 2020, surufatinib was approved in China for the treatment of advanced extra-pancreatic NETs based on data from the phase 3 SANET-ep trial (NCT02589821) which showed that the agent improved PFS over placebo at 9.2 months vs 3.8 months, respectively (HR, 0.33; 95% CI, 0.22-0.50; P <.0001).3,4
Most recently, in May 2021, the rolling submission of a new drug application for surufatinib to the FDA for the agent’s use in patients with pNETs and extra-pancreatic NETs was completed; the application was supported by data from SANET-p and SANET-ep.5