KEY TAKEAWAYS
- The phase III study determined the efficacy of CABO in previously treated pts with advanced epNET or pNET.
- The study’s primary endpoints included PFS, with preplanned interim assessments for futility after 33% and 66% of events and alpha spending of 0.001 per interim analysis. Secondary endpoints were RR, OS, and safety.
- The study showed that CABO improved PFS in epNET and pNET.
Inhibitors of the VEGF pathway have shown activity against NET. Researchers evaluated how well cabozantinib (CABO), an inhibitor that targets multiple kinases including VEGFR, c-MET, AXL, and RET, performed in treating patients (pts) who have previously received treatments for advanced forms of either extra-pancreatic NET (epNET) or pancreatic NET (pNET).
Patients with either locally advanced or metastatic well-to-moderately differentiated epNET or pNET were divided into two cohorts and randomly assigned in a 2:1 ratio to receive either 60 mg of CABO daily or a placebo. To qualify, participants had to show disease progression based on RECIST criteria within the last 12 months and have undergone at least one prior treatment, such as everolimus, sunitinib, or Lu-177 dotatate.
The randomization was adjusted based on whether pts were concurrently taking a somatostatin analog and by the primary site of the tumor in epNET or previous use of sunitinib in pNET cases. The study’s main objective was to measure progression-free survival (PFS), with interim assessments planned after 33% and 66% of predetermined events had occurred. An alpha level of 0.001 was set for each of these interim analyses. Secondary goals were response rate (RR), overall survival (OS), and safety.
Between October 2018 and June 2023, 197 pts with epNET (129 on CABO, 68 on placebo) and 93 pts with pNET (62 on CABO, 31 on placebo) were enrolled in the study. Of the epNET group, 55% had a primary tumor in the midgut or of unknown origin, and 70% were also taking a somatostatin analog (SSA). For the pNET group, 55% were on SSA, and 28% had previously been treated with sunitinib. The median duration of follow-up was 12.6 months for epNET pts and 10.1 months for pNET pts.
An independent Data Safety Monitoring Board (DSMB) reviewed the interim analysis for PFS, which was based on local radiology evaluations. For epNET, this was the second interim analysis with 109 events; for pNET, it was the first with 50 events. Both cohorts showed a significant improvement in PFS for those on CABO compared to the placebo group. No additional safety concerns arose. Consequently, the DSMB decided to halt further patient recruitment and to disclose the treatment details to participants on July 28, 2023. Additional data on response rates and overall survival will be released later.
CABO showed statistically significant and clinically meaningful improvements in PFS for both epNET and pNET pts. It may be a potential new therapy for pts with previously treated progressive NET.
Source: https://cslide.ctimeetingtech.com/esmo2023/attendee/confcal/show/session/82
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03375320
Chan, J. Alliance A021602: Phase III, Double-Blinded Study of Cabozantinib Versus Placebo for Advanced Neuroendocrine Tumors (NET) After Progression on Prior Therapy (CABINET).
