In a French noncomparative phase II trial (PRODIGE 59-FFCD 1707-DURIGAST) reported in JAMA Oncology, Tougeron et al found limited activity of FOLFIRI (leucovorin, fluorouracil, and irinotecan) plus durvalumab or durvalumab/tremelimumab in the second-line treatment of advanced gastric/gastroesophageal junction adenocarcinoma.
Study Details
In the multicenter trial, 96 patients were randomly assigned between August 2020 and June 2021 to receive FOLFIRI plus durvalumab (FD group, n = 48) or FD plus tremelimumab (FDT group, n = 48). Treatment consisted of:
- FOLFIRI as leucovorin at 400 mg/m2, fluorouracil bolus of 400 mg/m2 and continuous infusion of 2,400 mg/m2, and irinotecan at 180 mg/m2 every 2 weeks
- Durvalumab at 1,500 mg every 4 weeks
- Tremelimumab at 75 mg every 4 weeks for four cycles.
Treatment was continued, except as otherwise noted, until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed progression-free survival at 4 months; a treatment was considered effective if the 90% confidence interval in the treatment group included 70%.
Key Findings
Progression-free survival at 4 months was 44.7% (90% confidence interval [CI] = 32.3%–57.7%) in the FD group and 55.6% (90% CI = 42.3%–68.3%) in the FDT group, with the primary endpoint not being met in either group.
In the FD and FDT groups, median progression-free survival was 3.8 and 5.4 months, the objective response rate was 34.7% and 37.7%, and median overall survival was 13.2 and 9.5 months, respectively. Disease control for > 1 year was observed in 14.9% and 24.4% of patients.
Among all patients, a PD-L1 combined positive score (CPS) ≥ 5 was observed in 18 and a PD-L1 tumor proportion score (TPS) ≥1% was seen in 13. Median progression-free survival was 3.6 months for patients with a CPS ≥ 5 vs 5.4 months for those with a CPS < 5. In contrast, median progression-free survival was 6.0 months in patients with TPS ≥ 1% vs 3.8 months for those with TPS < 1%.
Grade ≥ 3 treatment-related adverse events were observed in 47.8% of patients in each group. The most common were fatigue (17.4%), decreased neutrophils (15.2%), and anemia (10.9%) in the FD group and fatigue (28.3%), decreased neutrophils (23.9%), diarrhea (10.9%), and nausea (10.9%) in the FDT group. No treatment-related deaths were reported.
The investigators concluded, “[The] combination of immune checkpoint inhibitors with FOLFIRI in second-line treatment for advanced gastric/gastroesophageal junction adenocarcinoma showed an acceptable safety profile but antitumor activity only in a subgroup of patients.”
David Tougeron, MD, PhD, of the Department of Gastroenterology and Hepatology, Poitiers University Hospital, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was funded by AstraZeneca. For full disclosures of the study authors, visit jamanetwork.com.
