Three-year ATTRACTION-2 follow-up results confirm the long-term efficacy of nivolumab in patients with previously treated advanced gastric/gastroesophageal junction (GEJ) cancer.
The ATTRACTION-2 study was a randomized, double-blind, phase 3 multicenter clinical trial of adult patients with refractory or previously treated unresectable advanced or recurrent gastric or gastroesophageal junction (GEJ) cancer. It demonstrated the efficacy of nivolumab, a PD-1 inhibitor, as third-line or later treatment in patients with advanced gastric or GEJ cancer. Immune checkpoint inhibitors (ICIs) such as nivolumab have demonstrated long-term efficacy in other cancer types, namely melanoma and lung cancer, but for advanced gastric or GEJ cancer, there are no studies reporting on the long-term efficacy of ICIs. ICIs are also associated with cancer pseudoprogression, where activated lymphocytes accumulate in tumors, giving the appearance of tumor enlargement. This makes pseudoprogression hard to distinguish from true tumor progression. Treatment beyond progression (TBP) after the first event of progressive disease in participants was allowed in the ATTRACTION-2 study because of this phenomenon.
In the ATTRACTION-2 trial, 601 patients were treated with either 3 mg/kg nivolumab intravenously or with a placebo every 2 weeks for 6 weeks. The primary study end point was overall survival (OS). Response was evaluated by computed tomography (CT) or magnetic resonance imaging (MRI) every treatment cycle for the first 10 cycles. This was continued until disease progression or toxicity required permanent discontinuation of treatment. Thereafter, CT or MRI response evaluation was performed every 2 weeks until the patient had permanent treatment discontinuation for any reason. If the patient met certain criteria at the first occurrence of disease progression, they were allowed TBP. At 3-year analysis, the median OS was 5.26 months in the nivolumab group and 4.14 months in the placebo group, with 3-year OS rates of 5.6% for the nivolumab group and 1.9% for the placebo group. The risk for death was significantly lower for the patient group receiving nivolumab. The median progression-free survival (PFS) was 1.61 months in the nivolumab group compared with 1.45 months in the placebo group. The PFS rates were 2.4% in the nivolumab group and 0% in the placebo group. Consistently higher PFS rates were seen in the nivolumab group after 2 months from treatment start. No patient in the placebo group achieved complete or partial responses. In the nivolumab group, 32 patients achieved complete or partial responses and the median duration of response was 10.12 months, with a median OS of 26.68 months. There were 3 patients in the nivolumab group who had a complete response and all survived longer than 3 years. In the TBP patient cohort (146 patients), the median duration of TBP for the nivolumab group was 1.12 months, with a range of 0 to 36.5 months. For the placebo group, TBP duration was 1.08 months, with a range of 0 to 11.1 months. Post-progression survival was a median of 5.8 months for the nivolumab group and 4.5 months for the placebo group. No new treatment-related adverse events developed after the 2-year study follow-up.
When used as treatment beyond progression, nivolumab gave patients with advanced gastric or GEJ cancer a survival advantage.
Source: Boku N, Satoh T, Ryu MH, et al. Nivolumab in previously treated advanced gastric cancer (ATTRACTION-2): 3-year update and outcome of treatment beyond progression with nivolumab. Gastric Cancer. 2021;24:946-958.