Panitumumab Plus Fluorouracil and Folinic Acid Versus Fluorouracil and Folinic Acid Alone as Maintenance Therapy in RAS Wild-Type Metastatic Colorectal Cancer: The Randomized PANAMA Trial (AIO KRK 0212).

PURPOSE: The randomized PANAMA trial investigated the efficacy of panitumumab (Pmab) when added to maintenance therapy with fluorouracil and folinic acid (FU/FA) in patients with RAS wild-type metastatic colorectal cancer. METHODS: Following first-line induction therapy with six cycles of FU/FA and oxaliplatin plus Pmab, responding patients (stable disease or partial or complete remission) were randomly assigned (1:1, open-label) to maintenance treatment with either FU/FA plus Pmab or FU/FA alone. The primary objective was to demonstrate superiority of progression-free survival (PFS, time from random assignment until progression or death) in favor of FU/FA plus Pmab with a hazard ratio (HR) of 0.75, a power of 80%, and a significance level of 10%. Secondary end points included overall survival, objective response rate of maintenance therapy, and toxicity. Survival end points were analyzed by the Kaplan-Meier method and compared by log-rank test and Cox regressions. Dichotomous variables were compared by Fisher's exact test; odds ratios were indicated when appropriate. The trial is registered with ClinicalTrials.gov (NCT01991873). RESULTS: Overall, 248 patients were randomly assigned and received maintenance therapy with either FU/FA plus Pmab (125 patients) or FU/FA alone (123 patients). At data cutoff, with 218 events (of 218 needed), PFS of maintenance therapy was significantly improved with FU/FA plus Pmab (8.8 months v 5.7 months; HR, 0.72; 80% CI, 0.60 to 0.85; P = .014). Overall survival (event rate 54%) numerically favored the FU/FA plus Pmab arm (28.7 months v 25.7 months; HR, 0.84; 95% CI, 0.60 to 1.18; P = .32). Objective response rates were 40.8% in patients receiving FU/FA plus Pmab versus 26.0% in patients receiving FU/FA alone (odds ratio, 1.96; 95% CI, 1.14 to 3.36; P = .02). The most frequent Common Terminology Criteria for Adverse Event grade ≥ 3 event during maintenance therapy was skin rash (7.2%). CONCLUSION: In RAS wild-type metastatic colorectal cancer, maintenance therapy with FU/FA plus Pmab induced a significantly superior PFS compared with FU/FA alone. If active maintenance therapy is aspired following induction therapy with FU/FA and oxaliplatin plus Pmab, FU/FA plus Pmab appears to be the most favorable option.

Endoscopic treatment of duodenal obstruction due to a gallstone ("Bouveret's syndrome").

We describe the case of a 73-year-old woman was admitted to our hospital because of constant abdominal pain in her right upper quadrant and postprandial bloating and fullness for several months. On abdominal x-ray the extrahepatic bile ducts were positive for gas and on ultrasound a gallstone in the duodenum was suspected whereas the gallbladder was not detectable. An upper gastrointestinal endoscopy confirmed a large gallstone that was impacted in the duodenal bulb ("Bouveret's syndrome"). The gallstone was fragmented employing mechanical lithotripsy and removed. Duodenoscopy revealed a cholecystoduodenal fistula and a second gallstone in the gallbladder. The patient underwent open cholecystectomy with closure of the cholecystoduodenal fistula and made a full recovery. We conclude that in patients with upper abdominal pain and pneumobilia on x-ray the unusual complication of cholelithiasis with an impacted gallstone in the duodenal bulb should be suspected. In those rare cases of Bouveret's syndrome endoscopic removal of the gallstone should be attempted to minimize the necessary surgical procedure whenever possible.