Regorafenib offers survival benefit for patients with pre-treated gastric cancer

Regorafenib outperformed placebo in terms of overall survival in patients with refractory, advanced gastric or oesophago-gastric junction cancer (AGOC) in the phase 3 INTEGRATE IIa trial, providing a new treatment option for this patient population. The phase 3 INTEGRATE IIb trial is currently ongoing to compare regorafenib plus nivolumab with chemotherapy in patients with refractory AGOC.

“The treatment options for patients with pre-treated AGOC are limited,” said Prof. Nick Pavlakis (University of Sydney, Australia) at the start of his presentation [1]. “However, regorafenib showed promising anti-tumour activity in a phase 2 trial [2].” After these findings had been reported, a phase 3 study was designed to test regorafenib against placebo. The INTEGRATE IIa trial (NCT02773524) randomised 251 patients with AGOC who had received at least 2 prior lines of therapy 2:1 to regorafenib, 160 mg, once daily at days 1 to 21 of a 28-day cycle, or placebo [3]. The primary endpoint was the overall survival (OS).

Patients in the regorafenib arm had an OS benefit compared with patients in the placebo arm (HR 0.68; 95% CI 0.52–0.90; P=0.006; see Figure) . The corresponding 12-month OS rates were 19% and 6%, respectively. Prof. Pavlakis mentioned that there were no significant differences among pre-defined subgroups. Furthermore, the progression-free survival results confirmed the OS results, demonstrating a benefit for patients on regorafenib over patients on placebo (HR 0.53; 95% CI 0.40–0.70; P<0.0001). Interestingly, patients receiving regorafenib displayed a significant delay in the deterioration of their global quality-of-life compared with patients receiving placebo (P=0.0043). According to Prof. Pavlakis, the safety profile of regorafenib was comparable with that of previously reported studies on this agent.

Figure: Overall survival of regorafenib versus placebo [3]



In conclusion, regorafenib improved the health outcomes in patients with pre-treated AGOC, presenting itself as a new treatment option for the population. The agent is further assessed in combination with nivolumab against chemotherapy in an estimated 450 patients with AGOC who failed on at least 2 prior lines of therapy in the INTEGRATE IIb trial (NCT04879368).

1. Smyth EC, et al. Lancet. 2020;396:635–648.
2. Pavlakis N, et al. JCO. 2016;34:2728–2735.
3. Pavlakis N, et al. INTEGRATE IIa: A randomised, double-blind, phase III study of regorafenib versus placebo in refractory advanced gastro-oesophageal cancer (AGOC)—A study led by the Australasian Gastro-intestinal Trials Group (AGITG). Late-breaking abstract 294, ASCO GI 2023, 19–21 January, San Francisco, CA, USA.

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Posted on 17 March 202317 May 2024