Regorafenib plus avelumab in advanced gastroenteropancreatic neuroendocrine neoplasms: a phase 2 trial and...

Area of Science:

• Oncology
• Immunotherapy
• Gastroenterology

Background:

• Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) represent a diverse group of tumors with limited therapeutic strategies.
• Advanced GEP-NENs often exhibit resistance to existing treatments, necessitating novel therapeutic approaches.

Purpose of the Study:

• To evaluate the efficacy and safety of combining regorafenib (a multikinase inhibitor) with avelumab (a PD1 ligand 1 inhibitor) in patients with advanced GEP-NENs.
• To assess the objective response rate and progression-free survival in this patient population.

Main Methods:

• A phase 2 Bayesian study involving 47 participants with advanced, well-differentiated GEP-NENs or GEP neuroendocrine carcinomas.
• Participants received daily regorafenib (160 mg) and biweekly avelumab (10 mg/kg) over 28-day cycles.
• Efficacy was evaluated based on objective response rate and progression-free survival, with safety assessed through treatment-related adverse events.

Main Results:

• The 6-month objective response rate was 18% (95% CI: 8-31%), with a median progression-free survival of 5.5 months (95% CI: 3.6-8).
• Durable responses were observed, lasting a median of 16.6 months.
• Common treatment-related adverse events included fatigue, diarrhea, and palmar-plantar erythrodysesthesia, which were generally manageable.

Conclusions:

• The combination of regorafenib and avelumab demonstrates clinical potential in treating advanced GEP-NENs.
• Exploratory analyses suggest PD1 and indoleamine 2,3-dioxygenase 1 expression may be associated with treatment resistance.
• Further validation in randomized trials, alongside the identification of predictive biomarkers, is crucial for optimizing this therapeutic strategy.