A phase 2 clinical trial has revealed promising efficacy for ramucirumab in combination with somatostatin analog therapy for patients with advanced, progressive extra-pancreatic neuroendocrine tumors (NET). The study demonstrated significant survival benefits, marking a potential advancement in treatment options for this challenging disease.
The trial (NCT02795858) enrolled 43 evaluable patients, achieving a median progression-free survival (PFS) of 14.2 months (95% CI, 9.0-25.6 months) and a median overall survival of 24.9 months (95% CI, 20.7-43.1). The response data showed that 5% of patients achieved partial response, while 77% maintained stable disease.
Treatment Protocol and Patient Demographics
Patients received ramucirumab at 8 mg/kg intravenously on days 1 and 15 of 28-day cycles, combined with somatostatin analog therapy using either octreotide long-acting release depot or lanreotide. The study population had a median age of 64 years (range 36-77), with 56% male participants and 95% White patients. Most patients had primary tumors in the small intestine (46%) or lung (23%).
Prior Treatment Experience
The study included heavily pretreated patients, with 81% having prior exposure to somatostatin analog treatment. Other previous therapies included:
- Everolimus (56%)
- Cytotoxic chemotherapy (30%)
- VEGF pathway inhibitors (26%)
- Radiation therapy (28%)
- Peptide receptor radionuclide therapy (7%)
Safety and Tolerability
The safety profile was manageable, with hypertension being the most common treatment-related adverse event, affecting 84% of patients, including 35% experiencing grade 3 hypertension. Other grade 3 adverse events were relatively rare, including proteinuria and elevated liver enzymes.
"Treatment with ramucirumab was associated with encouraging efficacy in patients with advanced, progressive extra-pancreatic NET," stated Dr. Kimberly Perez, senior physician at Dana-Farber Cancer Institute and assistant professor at Harvard Medical School. "The median PFS duration of 14.2 months is consistent with what has been observed with other VEGF pathway inhibitors that have demonstrated activity in NET."
Clinical Implications
The results suggest that ramucirumab could play a significant role in the treatment landscape for NET patients. The combination therapy's efficacy, particularly in a population with limited treatment options, warrants further investigation of ramucirumab and other VEGF pathway inhibitors in this setting.
The study's findings are particularly noteworthy given that patients were allowed to have received multiple prior treatments, including anti-VEGF therapy, suggesting the combination's potential utility across various treatment lines. The trial continues to support the exploration of targeted therapies in neuroendocrine tumors, where treatment options have historically been limited.
