Ramucirumab/Somatostatin Displays Prolonged Survival in Advanced NET

A phase 2 trial revealed survival with ramucirumab plus somatostatin was consistent with other VEGF pathways in treating advanced neuroendocrine tumors.

Ramucirumab (Cyramza) in combination with somatostatin analog therapy elicited prolonged progression-free survival (PFS) outcomes in patients with advanced, progressive extra-pancreatic neuroendocrine tumors (NET), according to findings from a phase 2 trial (NCT02795858) published in The Oncologist.1

Efficacy findings from the trial reported that among the 43 efficacy evaluable patients, the median PFS of 14.2 months (95% CI, 9.0 months-25.6 months). Furthermore, the median overall survival (OS) was 24.9 months (95% CI, 20.7-43.1). Among this patient population, 5% (95% CI, 0.6%-15.8%) of patients experienced a partial response and 77% (95% CI, 61.4%-88.2%) experienced stable disease. An additional 7% (95% CI, 1.5%-19.1%) of patients had progressive disease, with the remaining 5 patients unavailable for restaging due to early withdrawal.

“Treatment with ramucirumab was associated with encouraging efficacy in patients with advanced, progressive extra-pancreatic NET. 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,” Kimberly Perez, MD, senior physician in Medical Oncology at the Dana-Farber Cancer Institute and assistant professor of Medicine at Harvard Medical School, wrote in the publication with study coinvestigators.1 “The results of our study and the ongoing efforts highlight a potential role for ramucirumab in the treatment of NET. Continued investigation of ramucirumab and other inhibitors of the VEGF pathway for the treatment of NET is warranted.”

Patients with histologically confirmed metastatic or locally advanced well- or moderately differentiated extra-pancreatic NET not amenable to curative resection (n = 43) were enrolled between July 1, 2016, and December 31, 2022, to receive ramucirumab plus somatostatin. There were no limits to prior treatments in this patient population, and prior anti-VEGF therapy was permitted unless discontinuation was related to unacceptable toxicity. Additionally, those enrolled were required to have documented disease progression within 12 months prior to enrollment.

Study treatment consisted of 8 mg/kg intravenous ramucirumab and somatostatin analog therapy with octreotide long-acting release depot or lanreotide on days 1 and 15 of 28-day cycles. Patients were allowed to initiate treatment with somatostatin during screening prior to starting ramucirumab if they were somatostatin analog naïve. Treatment with ramucirumab/somatostatin continued until progression, unacceptable toxicity, or withdrawal of consent.

Among patients enrolled on trial at baseline, the median age was 64 years (range, 36-77), 56% of patients were male, and 95% were White. Most patients had an ECOG performance status of 0 (42%) or 1 (53%), had primary tumors located in either their small intestine (46%) or lung (23%), and had prior exposure to somatostatin analog treatment (81%). Common prior therapies included everolimus (56%), cytotoxic chemotherapy (30%), other VEGF pathway inhibitors (26%), radiation therapy (28%), and peptide receptor radionuclide therapy (7%)

The primary end point of the trial was PFS. Secondary end point included OS, overall radiographic response, biochemical response utilizing serum chromogranin and 24-hour urine 5-HIAA, and toxicity.2

All 43 patients were evaluable for efficacy and experienced at least 1 treatment-related adverse event (TRAE). Furthermore, any-grade hypertension was reported in 36 (84%) patients, including 15 (35%) who experienced grade 3 hypertension while receiving ramucirumab. Additionally, only 5 of 15 patients who developed grade 3 hypertension did not have hypertension at baseline.

Other grade 3 TRAEs included 2 instances of proteinuria and elevated aspartate aminotransferase, and single instances of headache, diarrhea, elevated alanine aminotransferase, hyponatremia, hypokalemia, dyspnea, and syncope. No treatment-related deaths were reported with either ramucirumab or somatostatin analog therapy.

References

1. Perez K, Kulke MH, Zheng H, et al. A phase II study of ramucirumab and somatostatin analog therapy in patients with advanced neuroendocrine tumors. Oncologist. 2025;30(1):oyae364. doi:10.1093/oncolo/oyae364
2. A phase II study of ramucirumab with somatostatin analog therapy in patients with advanced, progressive carcinoid tumors. ClinicalTrials.gov. Updated March 5, 2024. Accessed January 22, 2025. https://clinicaltrials.gov/study/NCT02795858?tab=table