1147MO - Ramucirumab in combination with dacarbazine in patients with progressive well-differentiated metastatic pancreatic neuroendocrine tumors (RamuNET): An AIO phase II multicenter single-arm study

Background

Targeting tumor angiogenic agents represents an established therapeutic concept in advanced pancreatic neuroendocrine tumors. However, response rates, side effects and outcome data strongly vary among the established agents. The evaluation of combination regimens incorporating cytotoxic chemotherapy and novel antiangiogenic compounds is therefore urgently needed. The RamuNET trial aims to elucidate the effectiveness of a novel combination regimen using the alkylating agent dacarbazine and the VEGFR antibody ramucirumab in progressive advanced PanNET patients.

Methods

The RamuNET study is an investigator-initiated multicenter prospective single-arm trial to evaluate the efficacy of ramucirumab (8mg/kg q2w) in combination with DTIC (650mg/m² q4w). Patients with pancreatic NET G1-G3 and progressive disease after at least one standard regimen were eligible. The primary endpoint was disease control after 6 months.

Results

From October 2019 till June 2023, 45 patients with a median age of 59 years (range 39-80) have been enrolled. All patients had progressive disease. In two-thirds (n=29) of the cases, a recent histology was available. The majority of patients had a pancreatic NET G2 (n=35, 75.6%). Only 4 patients presented with a functionally active tumor (8.9%). Overall, 564 AEs were observed, of which 71 (12.6%) were classified as grade 3/4. Most frequent adverse events were gastrointestinal (19.3%), infectious (8.5%) and hematological (8.3%). In this preliminary evaluation, the disease-control rate was 71.1% (n=32) after 6 months. One complete response (2.2%) and seven partial responses (15.6%) were observed. During the first 6 months, nine patients were progressive and 4 patients were terminated early due to adverse events (n=13, 28.9%). Currently, 28 patients (62.2%) are still on study drug. In 17 (37.8%) cases end of treatment was reached.

Conclusions

The combination of DTIC and ramucirumab represents a safe and promising new treatment option in pre-treated pancreatic NET patients. The underlying mechanism of the combined treatment strategy will be investigated to identify markers predicting response to VEGFR2 inhibition.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Martin Luther University Halle-Wittenberg.

Funding

Eli Lilly.

Disclosure

All authors have declared no conflicts of interest.