Safety and Efficacy of Avelumab in Small Bowel Adenocarcinoma

Clin Colorectal Cancer. 2022 Sep;21(3):236-243. doi: 10.1016/j.clcc.2022.03.003. Epub 2022 Mar 24.


Introduction: Small bowel adenocarcinomas (SBAs) are rare and frequently treated like large intestinal adenocarcinomas. However, SBAs have a very different microenvironment and could respond differently to the same therapies. Our previous data suggested that SBAs might benefit from targeting the PD-1/PD-L1 axis based on PD-L1 staining in almost 50% of SBA tissue samples tested. Thus, we designed a phase 2 study to explore safety and efficacy of avelumab in SBA.

Patients and methods: Patients with advanced or metastatic disease were enrolled; ampullary tumors were considered part of the duodenum and allowed. Prior PD-1/PD-L1 inhibition was not allowed. Avelumab (10 mg/kg) was given every 2 weeks, and imaging was performed every 8 weeks. Primary endpoint was response rate.

Results: Eight patients (n = 5, small intestine; n = 3, ampullary) were enrolled, with a majority (88%) being male and a median age of 61 years. Of 7 efficacy-evaluable patients, 2 (29%) experienced partial responses; stable disease occurred in 3 additional patients (71%). Median progression-free survival was 3.35 months. Most frequent, related toxicities were anemia, fatigue, and infusion-related reaction (25% each), mostly grade ≤2; grade 3 hypokalemia and hyponatremia occurred in one patient, and another reported grade 4 diabetic ketoacidosis.

Conclusions: Despite the observed benefit, accrual was slower than expected and the study was closed early due to feasibility. A general clinic observation was that patients were receiving immunotherapy off-label as the availability of these agents increased. Off-label availability and disease rarity were likely drivers of insufficient accrual.

Keywords: Immune checkpoint inhibition; Immunotherapy; PD-L1; Rare tumor; Small intestine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma* / drug therapy
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Humanized
  • B7-H1 Antigen*
  • Female
  • Humans
  • Intestine, Small
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor
  • Tumor Microenvironment


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • B7-H1 Antigen
  • Programmed Cell Death 1 Receptor
  • avelumab