Regorafenib plus nivolumab and chemotherapy has shown “promising activity” as first-line treatment in patients with HER2-negative metastatic esophagogastric cancer, according to researchers.

In a phase 2 trial, patients who received this combination had a median progression-free survival (PFS) of 13 months, and the median overall survival (OS) was not reached at a median follow-up of 18 months.

These findings were published in The Lancet Oncology.

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The trial ( Identifier: NCT04757363) included 39 patients with previously untreated, HER2-negative, metastatic esophagogastric cancer who received study treatment. The patients received fluorouracil as a 400 mg/m² bolus followed by 2400 mg/m² over 48 hours, leucovorin at 400 mg/m², oxaliplatin at 85 mg/m², and nivolumab at 240 mg on days 1 and 15 of a 28-day cycle. They also received regorafenib at 80 mg on days 1-21. Patients continued treatment until disease progression, unacceptable toxicity, or withdrawal of consent.

The efficacy analysis included 35 patients who had gastric cancer (46%), esophageal cancer (31%), or gastroesophageal junction cancer (23%). Their median age at baseline was 57 years, 74% were men, and 80% were White.

At a median follow-up of 18.1 months, the median PFS was 13.0 months, and the median OS was not reached. The PFS rate was 71% at 6 months and 51% at 12 months. The OS rate was 97% at 6 months and 85% at 12 months.

In the 29 patients who had measurable disease at baseline, the objective response rate was 76%. Three patients had a complete response, and 19 had a partial response. The median duration of response was 17.0 months.

The safety population included 39 patients. The rate of adverse events (AEs) was 97%. The most common AEs were fatigue (92%); paresthesia or peripheral neuropathy (77%); palmar-plantar erythrodysesthesia syndrome (67%); constipation (67%); anorexia or dysgeusia (64%); abdominal pain (64%); and dry skin, pruritus, or rash (64%).

The rate of grade 3 or higher AEs was 79%. The most common of these were decreased neutrophil count (46%); hypertension (15%); dry skin, pruritus, or rash (13%); and anemia (10%). There were no fatal AEs related to treatment.

“Regorafenib can be safely combined with nivolumab and chemotherapy and showed promising activity in HER2-negative metastatic esophagogastric cancer,” the researchers wrote. “A randomized, phase 3 clinical trial is planned.”

Disclosures: This research was partly supported by Bristol Myers Squibb and Bayer. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Cytryn SL. Moy RH, Cowzer DC, et al. First-line regorafenib with nivolumab and chemotherapy in advanced oesophageal, gastric, or gastro-oesophageal junction cancer in the USA: A single-arm, single-centre, phase 2 trial. Lancet Oncol. Published online September 1, 2023. doi:10.1016/S1470-2045(23)00358-3