Nivolumab Monotherapy in Advanced Gastroesophageal or Gastric Cancer

Patients with gastric cancer/gastroesophageal cancer (GC/GEC) often present with advanced or metastatic disease, a diagnosis associated with poor prognosis, with 1-year survival ~20%, and few treatment options. Nivolumab is a fully human anti–PD-1 IgG4 monoclonal antibody with a favorable safety profile and demonstrated efficacy in melanoma, non–small-cell lung cancer, and renal-cell carcinoma.1-3 Le and colleagues reported initial results for patients with GC/GEC receiving nivolumab monotherapy (3 mg/kg intravenously every 2 weeks) and treated until disease progression or intolerable toxicity.4 The primary end point was objective response rate (ORR); other end points included safety, progression-free survival, overall survival (OS), and biomarker status. 

A total of 59 patients were enrolled and treated with single-agent nivolumab; 83% of the patients had received 2 or more prior lines of therapy. At database lock, 7% of the patients were on active treatment; 93% of the patients had discontinued (disease progression, n = 46; unrelated adverse events, n = 6; treatment-related adverse events [TRAEs], n = 2; other, n = 3). The ORR was 14% (1 complete response, 7 partial responses); 11 (21%) patients had stable disease, and 34 (58%) had progressive disease. Among responders, the median duration of response was 7.1 months Median OS was 5.0 months (95% CI, 3.4-12.4); and the 12-month OS rate was 36% (95% CI, 21-51). The objective response rate (ORR) in patients with PD-L1 positive (≥1% cutoff) was 27% compared to 12% in those with PD-L1- tumors. In those with PD-L1+ tumors (≥5% cutoff), the ORR was 33% compared with 15% in those with <5% PD-L1 expression. At 6 and 12 months, 49% and 36%, respectively, of the patients were still alive.

Grade 3/4 treatment-related adverse events (TRAEs) occurred in 14% of patients and included pneumonitis, fatigue, diarrhea, vomiting, hypothyroidism, and increased aspartate and alanine aminotransferase and alkaline phosphatase levels. No grade 5 TRAEs or treatment-related deaths occurred. This study showed that nivolumab monotherapy was well-tolerated and demonstrated encouraging antitumor activity in heavily pretreated, chemotherapy-refractory patients with metastatic GC/GEC. While objective responses occurred in patients with PD-L1–positive and –negative tumors, a higher percentage of patients with PD-L1+ tumors responded to nivolumab therapy.

  1. Larkin J, et al. N Engl J Med. 2015;373:1803-13.
  2. Gettinger SN, et al. ASCO 2015. Abstract 8025.
  3. Hammers HJ, et al. ASCO 2015. Abstract TPS4578.
  4. Le DT, et al. ASCO 2016 Gastrointestinal Cancers Symposium. Abstract 6.