ATTRACTION-2 Points to Nivolumab For Advanced Gastric Cancer

Nivolumab may offer a novel strategy for advanced gastric or gastro-oesophageal junction cancer refractory to at least two prior lines of chemotherapy

medwireNews: Nivolumab extends overall survival (OS) for heavily pretreated, unresectable gastric or gastro-oesophageal junction cancer compared with placebo, indicate phase III trial results from patients in Japan, South Korea and Taiwan.

Median OS was 5.26 months for the 330 participants randomly assigned to receive nivolumab 3 mg/kg every 2 weeks versus 4.14 months for the 163 patients who were given placebo, giving a significant hazard ratio of 0.63, the ATTRACTION-2 investigators report in The Lancet.

The authors say there was “a persistent survival advantage with nivolumab”, citing Kaplan-Meier estimates showing an OS benefit with the programmed cell death protein 1 (PD-1) inhibitor versus placebo at 6 months (46.1 vs 34.7%), 12 months (26.2 vs 10.9%) and 18 months (16.2 vs 5.0%).

And they emphasize that nivolumab’s efficacy is of “particular note” as all participants had disease refractory to, or were intolerant of, at least two previous chemotherapy regimens and around 80% had received three or more lines of therapy.

“These findings suggest that nivolumab could be a standard-of-care treatment option and support ongoing assessment of nivolumab, alone and in combination with other treatments in earlier lines of therapy, in patients with advanced gastric or gastro-oesophageal junction cancer”, conclude Narikazu Boku, from National Cancer Center Hospital in Tokyo, Japan, and co-authors.

Writing in a linked comment, however, Ian Chau, from Royal Marsden Hospital in Surrey, UK, cautions that differences in gastric cancer gene expression between Asian and nonAsian patients mean the ATTRACTION-2 results “might not be applicable to European or North American populations.”

Exploratory analysis of a subgroup of 192 patients with tissue samples indicated that the OS benefit with nivolumab was not linked to tumours having programmed cell death ligand 1 (PD-L1) expression of at least 1%, although the researchers urge cautious interpretation of results from a small number of PD-L1-positive patients.

And exploratory post-hoc analysis indicated that nivolumab was associated with an OS advantage over placebo regardless of whether or not patients had prior use of the anti-angiogenesis agent ramucirumab.

Safety findings suggested that nivolumab was tolerable, with any-grade treatment-related adverse events reported in 43% of nivolumab-treated patients and 27% of controls, with corresponding rates of grade 3–4 events at 10% versus 4%. Such events led to treatment discontinuation in 3% and 2% of patients, respectively.

But noting that almost half of patients in the nivolumab arm received only one cycle of the drug and fewer than a fifth continued treatment for at least 6 months, Ian Chau suggests that the total number of doses may have been too few for immune-related adverse reactions to present.

“The ongoing randomised controlled trials of nivolumab and pembrolizumab in earlier line treatment should define more accurately the incidence of immune-related toxicities in gastric cancer after prolonged exposure to these PD-1 and [PD-L1] antibodies”, he concludes.


Kang Y-K, Boku N, Satoh T, et al. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet; Advance online publication 6 October 2017. DOI:

Chau I. Checkpoint inhibition: an ATTRACTION in advanced gastric cancer? Lancet; Advance online publication 6 October 2017. DOI:

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