Sunitinib and Evofosfamide (TH-302) in Systemic Treatment-Naïve Patients with Grade 1/2 Metastatic Pancreatic Neuroendocrine Tumors: The GETNE-1408 Trial.
Enrique GrandeCristina Rodriguez-AntonaCarlos LópezTeresa Alonso-GordoaMarta BenaventJaume CapdevilaAlex TeuléAna CustodioIsabel SevillaJorge HernandoPablo GajateJavier Molina-CerrilloJuan José DíezMaría SantosJavier LanillosRocío García-CarboneroPublished in: The oncologist (2021)
SUN plus EVO had a negative toxicity profile that should be taken into account for further clinical research in advanced panNETs. The combination showed moderate activity in terms of treatment response that did not correlate with somatic mutations. (Clinical trial identification number: NCT02402062) IMPLICATIONS FOR PRACTICE: Addition of hypoxia-activated prodrugs has been proposed as a potential mechanism to overcome tumor resistance to antiangiogenic agents. Sunitinib and evofosfamide, which were widely proposed as a potential synergistic option, showed modest efficacy in pancreatic neuroendocrine tumors (panNETs), reaching a median objective response rate of 17.6% and median progression-free survival of 10.4 months. Treatment response does not correlate with the biomarkers analyzed. The high systemic toxicity, with 88.2% of patients discontinuing the treatment, makes this therapeutic approach unfeasible and encourages future research to overcome panNETs' resistance to antiangiogenic agents with other therapies with a safer profile.
Keyphrases
- neuroendocrine tumors
- clinical trial
- free survival
- end stage renal disease
- oxidative stress
- newly diagnosed
- primary care
- chronic kidney disease
- phase ii
- metastatic renal cell carcinoma
- endothelial cells
- high intensity
- gene expression
- risk assessment
- dna methylation
- randomized controlled trial
- copy number
- human health
- quality improvement
- double blind