2017 GI Cancers Symposium: Nivolumab Demonstrated Efficacy and Improved Survival in Patients With Previously Treated Advanced Gastric Cancer

Key Points

  • Median overall survival was 5.32 months for patients treated with nivolumab, compared to 4.14 months for those treated with placebo.
  • In addition, the 12-month overall survival in the nivolumab group was 26.6% vs 10.9% in the placebo group.
  • Patients treated with nivolumab also experienced an objective response rate of 11.2% compared to 0% with placebo and a median duration of response of 9.53 months, which were secondary endpoints.

Results of the ONO-4538-12 trial demonstrated that nivolumab (Opdivo) significantly reduced the risk of death by 37% (hazard ratio [HR] = 0.63; < .0001) in patients with previously treated advanced gastric cancer refractory to or intolerant of standard therapy, a condition without current standard-of-care treatments, according to an abstract presented by Kang et al at the 2017 Gastrointestinal Cancers Symposium in San Francisco (Abstract 2).

Major Findings

ONO-4538-12 is a phase III, randomized, double-blind, placebo-controlled clinical trial evaluating nivolumab’s efficacy and safety in such patients. The primary endpoint of the study is overall survival. Median overall survival was 5.32 months (95% confidence interval [CI] = 4.63–6.41) for patients treated with nivolumab, compared to 4.14 months (95% CI = 3.42–4.86, < .0001) for those treated with placebo. In addition, the 12-month overall survival in the nivolumab group was 26.6% (95% CI = 21.1­–32.4) vs 10.9% (95% CI = 6.2­­–17.0) in the placebo group.

Patients treated with nivolumab also experienced an objective response rate of 11.2% (95% CI = 7.7­–15.6) compared to 0% (95% CI = 0.0–2.8) with placebo and a median duration of response of 9.53 months (95% CI = 6.14–9.82), which were secondary endpoints.

The safety profile of nivolumab was consistent with previously reported studies in solid tumors. Treatment-related adverse events of any grade and grade 3/4 occurred in 42.7% vs 26.7% and 10.3% vs 4.3% of nivolumab-treated and placebo-treated patients, respectively. The grade 3/4 treatment-related adverse events reported in more than 2% of patients were diarrhea, fatigue, decreased appetite, pyrexia, as well increased AST and ALT in the nivolumab group and fatigue and decreased appetite in the placebo group. The nivolumab and placebo-treated patients had similar rates of treatment-related adverse events leading to discontinuation—2.7% and 2.5%, respectively.

“ONO-4538-12 is the first randomized, phase 3 immuno-oncology trial to demonstrate improved survival for patients with previously treated advanced or recurrent gastric cancer. We find these results with nivolumab encouraging, as gastric cancer is a leading cause of cancer death globally and unmet needs remain for patients with advanced forms of this disease who become intolerant to chemotherapy or for whom such treatment has failed,” said Ian M. Waxman, MD, Development Lead, Gastrointestinal Oncology, Bristol-Myers Squibb.

“These results show a clinical benefit with nivolumab for patients with pretreated advanced or recurrent gastric cancer and establish a strong basis for conducting additional studies with nivolumab as a treatment for patients with gastric cancer,” added lead study investigator Yoon-Koo Kang, MD, PhD, of the Department of Oncology at the University of Ulsan College of Medicine, Asan Medical Center in Seoul, Korea.

About ONO-4538-12

ONO-4538-12 (NCT02267343) is a phase III, randomized, double-blind, placebo-controlled clinical trial conducted in Japan, Korea, and Taiwan, evaluating the efficacy and safety of nivolumab in patients with unresectable, previously treated, advanced or recurrent gastric cancer, including gastroesophageal junction cancer, refractory to or intolerant of standard therapy. This trial was conducted by Ono Pharmaceutical Co. Ltd of Japan, Bristol-Myers Squibb’s development partner for nivolumab.

In ONO-4538-12, nivolumab at 3 mg/kg or placebo was administered every 2 weeks until disease progression or discontinuation due to unacceptable toxicity. The primary endpoint, overall survival, was assessed for the superiority of nivolumab vs placebo. The secondary endpoints included objective response rate, duration of response, progression-free survival, best overall response, time to response, disease control rate, and safety measures.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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