The addition of regorafenib to best supportive care improves outcomes in patients with advanced, refractory gastric or gastroesophageal junction (GEJ) cancer, according to results from a phase 3 trial presented at the 2023 ASCO Gastrointestinal Cancers Symposium.

“Regorafenib was shown to significantly improve survival, compared with placebo, in patients with refractory advanced gastroesophageal cancer, delaying deterioration in quality of life, prolonging progression-free survival, and with no new toxicity signals,” said study presenter Nick Pavlakis, MBBS, PhD, of Royal North Shore Hospital in St Leonards, New South Wales, Australia.

These results come from the phase 3 INTEGRATE IIa trial ( Identifier: NCT02773524), which began as the INTEGRATE II trial. Due to a change in practice, INTEGRATE II was split into INTEGRATE IIa (comparing regorafenib vs placebo) and INTEGRATE IIb (comparing regorafenib plus nivolumab vs chemotherapy).  

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INTEGRATE IIa included 251 patients with advanced gastric/GEJ cancer who had received at least 2 prior lines of treatment, including a platinum agent and a fluoropyrimidine analogue.

Patients were randomly assigned to receive regorafenib (n=169) or placebo (n=82). Both groups received best supportive care as well. Baseline characteristics were well balanced between the arms.

Overall survival (OS) was superior in the regorafenib arm (hazard ratio [HR], 0.68; 95% CI, 0.52-0.90; P =.006). The 12-month OS rate was 19% in the regorafenib arm and 6% in the placebo arm.

Patients in the regorafenib arm also had improved progression-free survival (HR, 0.53; 95% CI, 0.40-0.70; P <.0001). Furthermore, deterioration in global quality of life was delayed in the regorafenib arm compared with the placebo arm (P =.0043). 

The rate of grade 3 adverse events (AEs) was 55% with regorafenib and 37% with placebo. The rate of grade 4 AEs was 7% and 4%, respectively. The most common grade 3-4 AEs with regorafenib were fatigue, palmar-plantar erythrodysesthesia syndrome, and hypertension.

There were no fatal AEs in the placebo arm and 3 in the regorafenib arm. The cause of death was hepatic failure in 1 patient and sepsis in 2 patients.

The researchers also pooled data from the 251 patients in the INTEGRATE IIa trial with data from 152 patients who were enrolled in INTEGRATE II before the trial amendment. In this group, the OS was still superior with regorafenib (HR, 0.70; 95% CI, 0.56-0.87; P =.001).

These results suggest regorafenib is a new treatment option for these patients, Dr Pavlakis said. He added that the INTEGRATE IIb trial ( Identifier: NCT04879368) is ongoing. 

Disclosures: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Pavlakis N, Shitara K, Sjoquist KM, 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). ASCO GI 2023. January 19-21, 2023. Abstract LBA294.