FOLFIRI Plus Durvalumab With or Without Tremelimumab in Second-Line Treatment of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: The PRODIGE 59-FFCD 1707-DURIGAST Randomized Clinical Trial.

Importance: Efficacy of second-line chemotherapy in advanced gastric or gastrooesphageal junction (GEJ) adenocarcinoma remains limited. Ojectives: To determine the efficacy of 1 or 2 immune checkpoint inhibitors combined with FOLFIRI (leucovorin [folinic acid], fluorouracil, and irinotecan) in the treatment of advanced gastric/GEJ adenocarcinoma. Design, Setting, and Participants: The PRODIGE 59-FFCD 1707-DURIGAST trial is a randomized, multicenter, noncomparative, phase 2 trial, conducted from August 27, 2020, and June 4, 2021, at 37 centers in France that included patients with advanced gastric/GEJ adenocarcinoma who had disease progression after platinum-based first-line chemotherapy. Intervention: Patients were randomized to receive FOLFIRI plus durvalumab (anti-programmed cell death 1 [PD-L1]) (FD arm) or FOLFIRI plus durvalumab and tremelimumab (anti-cytotoxic T-lymphocyte associated protein 4 [CTLA-4]) (FDT arm). The efficacy analyses used a clinical cutoff date of January 9, 2023. Main outcome and Measures: The primary end point was progression-free survival (PFS) at 4 months according to RECIST 1.1 criteria evaluated by investigators. Results: Overall, between August 27, 2020, and June 4, 2021, 96 patients were randomized (48 in each arm). The median age was 59.7 years, 28 patients (30.4%) were women and 49 (53.3%) had GEJ tumors. Four month PFS was 44.7% (90% CI, 32.3-57.7) and 55.6% (90% CI, 42.3-68.3) in the FD and FDT arms, respectively. The primary end point was not met. Median PFS was 3.8 and 5.4 months, objective response rates were 34.7% and 37.7%, and median overall survival was 13.2 and 9.5 months in the FD and FDT arms, respectively. Disease control beyond 1 year was 14.9% in the FD arm and 24.4% in the FDT arm. Grade 3 to 4 treatment-related adverse events were observed in 22 (47.8%) patients in each arm. A combined positive score (CPS) PD-L1 of 5 or higher was observed in 18 tumors (34.0%) and a tumor proportion score (TPS) PD-L1 of 1% or higher in 13 tumors (24.5%). Median PFS according to CPS PD-L1 was similar (3.6 months for PD-L1 CPS ≥5 vs 5.4 months for PD-L1 CPS <5) by contrast for TPS PD-L1 (6.0 months for PD-L1 TPS ≥1% vs 3.8 months for PD-L1 TPS <1%). Conclusions and Relevance: Combination of immune checkpoint inhibitors with FOLFIRI in second-line treatment for advanced gastric/GEJ adenocarcinoma showed an acceptable safety profile but antitumor activity only in a subgroup of patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03959293.

Comparison of cold biopsy forceps vs cold snare for diminutive colorectal polyp removal: A multicenter non-inferiority randomized controlled trial.

BACKGROUND: European guidelines recommends the use of cold snare polypectomy (CSP) for removal of diminutive colorectal polyps (DCP). However, for DCP < 4 mm cold biopsy forceps (CBF) may be optional. We aimed to compare the efficacy of CSP with CBF for removal of DCP in routine colonoscopy. METHODS: We conducted a multicenter non-inferiority randomized controlled trial. After screening, 123 patients were prospectively included and 180 DCPs were removed by either CBF or CSP after randomization (1:1). The primary end-point was the histological complete resection rate defined by negative additional biopsies taken from the edge of the polypectomy ulcer site. RESULTS: Among DCPs, 121 (67.2%) adenomas or sessile serrated lesions were considered for the analysis. Polyps were 4 [1-5] mm in size, mostly flat (55.4%) and located in the proximal colon (44.6%). The en bloc resection rate was higher in the CSP group than the CBF group (91.7% vs. 42.6%, p < 0.001). The histological complete resection rate was comparable in the two groups (93.33% vs 90.16%; p = 0.527), even for polyps < 4 mm (91.30% vs 91.30%; p = 1). All specimens were retrieved and there was no difference in terms of procedure times and adverse events. Finally, univariate analysis did not identify any potential factor associated with complete resection rate. CONCLUSION: In this study, CSP was comparable to CBF for the removal of DCP. Therefore, CBF may be considered as an alternative technique for resection of DCP, together with CSP, ClinicalTrials.gov registry (NCT04727918).

Development of a porcine model for assessment of mucosal repair following endoscopic resection of the lower gastrointestinal tract.

BACKGROUND AND AIMS: Endoscopic mucosal resection (EMR) is widely performed for the treatment of colorectal polyps. However, the pathophysiological mechanisms of mucosal repair, including in situations at high risk of post-polypectomy bleeding, remain largely unknown. The objective of our study was to develop a porcine model of EMR in the lower gastrointestinal tract to monitor mucosal wound healing over time. METHODS: Under general anesthesia, five large wounds were created in the lower gastrointestinal tract at different times, i. e. at day 0, 3, 7, 10, and 14, by multiband EMR, in each of the six pigs in the study. A colorectal resection was performed at day 14 and the animal euthanized. Repeated endoscopic and endomicroscopic examination, and histological analysis were performed. RESULTS: No complications occurred and all animals reached the study end point. The endoscopic aspect of wound healing evolved into different phases with first a fibrin deposit covering the wounds which then gave way to granulomatous tissue. The size of the wound regressed significantly as early as day 3. Re-epithelialization of the wound started from day 7, and neo-mucosal crypts appeared from day 10. The endomicroscopic analysis described a 'ground glass appearance' from day 3 and irregular crypts from day 10, which was consistent with histological data. Good agreement between macroscopic, endomicroscopic, and histological parameters of mucosal wound healing was observed in vivo. CONCLUSION: This study demonstrates for the first time the feasibility of an experimental in vivo porcine model of lower gastrointestinal endoscopic resections to monitor tissue repair. This model might be helpful to document pharmacological approaches for preventing complications of endoscopic procedures performed in humans.