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Checkpoint inhibition: an ATTRACTION in advanced gastric cancer? cancer, two non-randomised controlled trials6,7 indicate that checkpoint inhibition is efficacious. In the CHECKMATE 032 study,6 59 patients received nivolumab alone. Overall survival at 12 months was 39%, which compares favourably with that of 26% in ATTRACTION-2. Corroborative evidence was reported in the KEYNOTE-059 phase 2 study,7 which assessed pembrolizumab in the same setting. Of the 259 patients included in KEYNOTE-059,7 nearly half were enrolled in the USA and only 13% in east Asia. Similar to ATTRACTION-2, overall survival at 12 months was 23·4%; the objective response was 11·6%, which was almost identical to that of 11·2% with nivolumab in the ATTRACTION-2 study. The safety profile appeared favourable for nivolumab compared with placebo in ATTRACTION-2. Nearly half of patients received only one treatment cycle with nivolumab and less than 20% of patients received treatment for 6 months or more. However, unlike cytotoxic chemotherapy, the onset of immune-related adverse events can be delayed. Previous randomised controlled trials8 of nivolumab in patients with melanoma suggested median time to onset of immunerelated cutaneous reaction was 6 weeks, whereas median time to onset for gastrointestinal, pulmonary, and thyroid toxicities was 9–10 weeks, and 11–24 weeks for hepatic, renal, and other endocrine toxicities. Therefore,

www.thelancet.com Published online October 6, 2017 http://dx.doi.org/10.1016/S0140-6736(17)32131-1

Published Online October 6, 2017 http://dx.doi.org/10.1016/ S0140-6736(17)32131-1 See Online/Articles http://dx.doi.org/10.1016/ S0140-6736(17)31827-5

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Annually, more than 950 000 people are diagnosed with gastric or oesophagogastric junction cancer1—the third most lethal cancer worldwide2—for which there is a considerable unmet clinical need. Blockade of immune checkpoints has been successfully integrated into standard treatment regimens for several solid tumours.3 The ATTRACTION-2 study by Yoon-Koo Kang and colleagues4 in The Lancet is, to my knowledge, the first randomised, placebo-controlled, phase 3 trial of immune checkpoint blockade in gastrointestinal cancers. In this study of 493 patients who had received at least two previous lines of systemic therapy for advanced gastric or oesophagogastric junction adenocarcinoma, treatment with nivolumab (3 mg/kg every 2 weeks)—a monoclonal antibody against programmed death-1 (PD-1)—resulted in a significant improvement in overall survival. The risk of death was 37% lower in the nivolumab group than in the placebo group (hazard ratio 0·63, 95% CI 0·51–0·78; p

Checkpoint inhibition: an ATTRACTION in advanced gastric cancer?

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