According to results of the INTEGRATE IIa trial, regorafenib improved the survival of patients with advanced refractory gastroesophageal junction cancer, compared with placebo.

Results from this trial were presented on Thursday, January 19, 2023, at the American Society of Clinical Oncologists Gastrointestinal Cancers Symposium in San Francisco, CA, by Nick Pavlakis, MD, Royal North Shore Hospital, New South Wales, Australia.

Regorafenib is an oral multi-targeted tyrosine kinase inhibitor (TKI). In the INTEGRATE phase 2 trial, Dr Pavlakis wrote, regorafenib “prolonged progression-free survival (PFS) versus placebo across all regions/subgroups.” The aim of INTEGRATE IIa is to evaluate regorafenib’s ability to improve overall survival (OS).

In this double-blind, international phase 3 trial, 251 patients with gastric or gastroesophageal junction cancer who had previously treated with at least 2 lines of therapy were enrolled. Patients were stratified based on tumor location, geographic region, and prior VEGF inhibitor exposure. Patients were randomized on a 2-to-1 basis to either regorafenib (n = 169) or placebo (n = 82). The primary end point of the study was OS in the entire study population, with OS among the Asian sub-population as a key secondary objective. Other secondary end points included PFS, objective response rate, and safety.

The median overall survival of the regorafenib arm was 4.5 months, compared with 4.0 in the placebo group (hazard ratio [HR] = 0.70; 95% confidence interval [CI], 0.53 to 0.92; P = .011). The 12-month survival rate was 19% in the regorafenib arm, compared with 6% in the placebo arm. The median PFS was 1.8 months in the regorafenib arm vs 1.6 months in the placebo arm (HR = 0.70; 95% CI, 0.40 to 0.69; P < .0001). There was no statistically significant difference foun, 95%d between patients from Asian regions compared with those from non-Asian regions, or across any other pre-specified groups. In a pooled analysis, the median overall survival of the regorafenib arm was 5.0 months vs 4.1 months in the placebo arm (HR = 0.69; 95% CI, 0.56 to 0.87; P = .001). There were reports of new adverse events with regorafenib.

Dr Pavlakis et al concluded these results offer regorafenib as “a new treatment option” in this patient profile, adding, “This result creates a therapeutic platform for combination studies.”

Source:

Pavlakis N, Shitara K, Sjoquist KM, et al. INTEGRATE IIa: A randomized, double-blind, phase III study of regorafenib versus placebo in refractory advanced gastro-oesophageal cancer (AGOC)—A study led by the Australasion Gastro-intestinal Trials Group (AGITG). Presented at 2023 ASCO Gastrointestinal Cancers Symposium; January 19-21, 2023; San Francisco, CA. Abstract LBA294