The AXINET (GETNE 1107) trial was an international, randomized, double-blind, placebo-controlled, phase II/III study evaluating the efficacy and safety of axitinib in combination with long-acting octreotide for patients with advanced extrapancreatic neuroendocrine tumors (epNETs). The study enrolled patients aged 18 years and older with unresectable or metastatic G1-2 epNETs who had received up to two previous lines of treatment. From October 2011 to May 2019, 256 patients were randomly assigned (1:1) to receive either oral axitinib 5 mg twice daily or placebo, both in combination with intramuscular octreotide long-acting release 30 mg every 28 days, until disease progression or unacceptable toxicity. Randomization was stratified by primary tumor site, Ki-67 index (≤5% or >5%), and time from diagnosis (> or ≤12 months). The primary endpoint was investigator-assessed progression-free survival (PFS). Efficacy was also assessed by a blinded independent central review (BICR).
Investigator-assessed median PFS was 17.2 months (95% CI, 13.6 to 24.7) in the axitinib group versus 13.1 months (95% CI, 10.9 to 18.6) in the placebo group (hazard ratio [HR], 0.86; 95% CI, 0.65 to 1.15). The median PFS per BICR was 16.6 months (95% CI, 13.5 to 24.2) for axitinib versus 9.9 months (95% CI, 8.2 to 13.9) for placebo (HR, 0.71; 95% CI, 0.54 to 0.94; p = .017). The objective response rate (ORR) was significantly greater for axitinib per both investigator assessment (17.5% vs 4.6%; p = .001) and BICR (12.8% vs 3.2%; p < .005). The most common grade ≥3 toxicities in the axitinib group were hypertension (24.0% vs 9.2% with placebo) and diarrhea (13.6% vs 1.5% with placebo). The study concluded that axitinib significantly increased PFS per BICR assessment and ORR per both investigator and BICR assessment compared with placebo, although the primary study endpoint of investigator-assessed PFS was not met. The toxicity profile was manageable with no new safety concerns.
This study looked at a new approach for treating advanced neuroendocrine tumors (NETs) that start in places like the gut or lungs, not the pancreas. These are rare, slow-growing cancers where forming new blood vessels (angiogenesis) helps them survive. The trial tested whether adding a pill called axitinib, which blocks blood vessel growth, to the standard monthly hormone injection (octreotide) could help people live longer without their cancer getting worse.
256 patients who had already tried up to two other treatments were randomly assigned to get either axitinib plus the hormone shot, or a placebo pill plus the hormone shot. The main goal was to see if the axitinib group had longer progression-free survival (the time before the cancer started growing again). When doctors assessed the scans, the difference wasn't statistically clear. However, when a separate, blinded team of experts reviewed the scans, they found the axitinib group did have a longer period before growth—16.6 months versus 9.9 months. More people in the axitinib group also saw their tumors shrink significantly.
The trade-off was more side effects. Nearly a quarter of people on axitinib developed serious high blood pressure, and about 14% had serious diarrhea, though these were considered manageable. The study concluded that while the combination improved some outcomes, it did not meet its primary goal, and the benefit must be weighed against these added side effects.
What this means for you: Adding axitinib to standard therapy helped shrink tumors and, in one review, delayed growth, but caused more side effects like hypertension.
View Original Abstract ↓
PURPOSE: Angiogenesis plays an essential role in neuroendocrine tumors (NETs). This study evaluates efficacy and safety of axitinib in extrapancreatic (ep)-NETs.
PATIENTS AND METHODS: AXINET was an international, randomized, double-blind, placebo-controlled, phase II/III trial including patients age 18 years and older, with unresectable/metastatic G1-2 epNETs and up to two previous treatment lines. Patients were randomly assigned (1:1) to axitinib 5 mg or placebo, both orally twice a day, in combination with intramuscular octreotide long-acting release 30 mg once every 28 days until disease progression or unacceptable toxicity. Randomization was stratified by primary tumor site, Ki-67 index (≤5% or >5%), and time from diagnosis (> or ≤12 months). The primary end point was investigator-assessed progression-free survival (PFS). Efficacy was also assessed by a blinded independent central review (BICR).
RESULTS: From October 2011 to May 2019, 256 patients were assigned to axitinib (n = 126) or placebo (n = 130). Investigator-assessed median PFS was 17.2 months (95% CI, 13.6 to 24.7) versus 13.1 months (95% CI, 10.9 to 18.6) in the axitinib and placebo groups, respectively (hazard ratio [HR], 0.86 [95% CI, 0.65 to 1.15]). The median BICR PFS was 16.6 months (95% CI, 13.5 to 24.2) versus 9.9 months (95% CI, 8.2 to 13.9) in the axitinib and placebo groups, respectively (HR, 0.71 [95% CI, 0.54 to 0.94], = .017). Objective response rate (ORR) was significantly greater for axitinib per investigator assessment (17.5% 4.6%; = .001) and BICR (12.8% 3.2%; .005). Most common grade ≥3 toxicities were hypertension (24.0% 9.2%) and diarrhea (13.6% 1.5%).
CONCLUSION: Axitinib significantly increased PFS per BICR assessment and ORR both per investigator and BICR assessment compared with placebo, although the primary study end point was not met. Toxicity profile was manageable with no new safety concerns.