Avelumab in Advanced Gastric or Gastroesophageal Cancer

Patients with gastric cancer (GC) have a poor prognosis, with an observed 5-year survival rate of approximately 4%. Systemic chemotherapy yields only modest improvements in survival, and ramucirumab, used as monotherapy or in combination with chemotherapy, achieves a survival benefit over chemotherapy alone in the second-line setting. The programmed death-1 receptor (PD-1) and its ligand (PD-L1) are key therapeutic targets in the reactivation of the immune response against multiple cancers, and PD-L1 has been shown to be expressed in 14% to 51% of GC.1

Avelumab is a fully human anti–PD-L1 IgG1 antibody being investigated in clinical trials. Chung and colleagues reported the safety and clinical activity of avelumab in patients with advanced GC or gastroesophageal junction (GEJ) adenocarcinoma based on the level of PD-L1 expression.2 This was a subanalysis of the phase 1b JAVELIN study that enrolled patients who had progressed on prior therapy (≥2 lines [2L]) and those who had received first-line chemotherapy but had not yet progressed (switch-maintenance [Mn]). A total of 75 patients with GC/GEJ received avelumab 10 mg/kg every 2 weeks until confirmed progression, unacceptable toxicity, or withdrawal. Tumors were assessed every 6 weeks (using RECIST 1.1). The best overall response and progression-free survival (PFS) were evaluated.

Treatment-emergent adverse events (TEAEs) of any grade occurred in 47 (62.7%) patients; the most common (>10%) was infusion-related reactions (12 [16.0%], all grade 1/2). Nine (12.0%) patients reported a grade ≥3 TEAE, including fatigue (n = 2), thrombocytopenia (n = 2), and anemia (n = 2; each 2.7%). There was 1 treatment-related death (hepatic failure/autoimmune hepatitis).

Clinical responses were observed in 15% of patients (all partial responses) in the 2L population and in 7.3% in the Mn population, including 1 complete response. PD-L1 expression was evaluable in 55 patients, including in 3 patients with a partial response. Median PFS in the 2L group was 36.0 weeks (95% confidence interval [CI], 6.0-36.0) for PD-L1+ and 11.6 weeks (95% CI, 2.1-21.9) for PD-L1− patients (using a ≥1% cutoff for PD-L1 expression). In the Mn group, median PFS for PD-L1+ and PD-L1− status was 17.6 weeks (95% CI, 5.9-18.0) and 11.6 weeks (95% CI, 5.7-17.7), respectively. The authors concluded that single-agent avelumab showed an acceptable safety profile and promising clinical activity in GC/GEJ patients. Objective responses and disease stabilization were observed with both PD-L1+ and PD-L1– tumor types, but median PFS was longer in PD-L1+ patients. Additional clinical studies of avelumab, as a single agent or in combination with other agents, are under way in patients with GC/GEJ, including in first- and third-line settings.3,4



  1. De Guillebon E, et al. World J Gastroenterol. 2015;7:95-101.
  2. Chung HC, et al. ASCO 2016 Gastrointestinal Cancers Symposium. Abstract 167.
  3. Oh D-Y, et al. ASCO 2016 Gastrointestinal Cancers Symposium. Abstract TPS188.
  4. Nishina T, et al. ASCO 2016 Gastrointestinal Cancers Symposium. Abstract 168.