APACT

APACT randomised 866 treatment-naive patients with resected pancreatic ductal adenocarcinoma to nab-paclitaxel 125 mg/m2 with gemcitabine 1,000 mg/m2 or gemcitabine alone on days 1, 8 and 15 of six 28-day cycles; 287 of 432 and 310 of 434 completed treatment. At the primary cut-off (December 2018, median follow-up 38.5 months) independently assessed disease-free survival was 19.4 against 18.8 months (hazard ratio 0.88, 95 percent confidence interval 0.729 to 1.063; p 0.18), so the trial missed its primary endpoint; investigator-assessed disease-free survival was 16.6 against 13.7 months (hazard ratio 0.82; p 0.02). Overall survival favoured the combination at every cut: 40.5 against 36.2 months (hazard ratio 0.82; p 0.045) at the primary analysis and 41.8 against 37.7 months (hazard ratio 0.80; p 0.0091) at five years with 88 percent of events. Grade 3 or worse treatment-emergent adverse events occurred in 86 against 68 percent, with two treatment-related deaths per arm. The trial recruited at six UK sites (Addenbrooke's Cambridge, Glasgow Royal Infirmary and Weston Park Sheffield among them). Because the primary endpoint was missed the regimen sits below modified FOLFIRINOX and gemcitabine plus capecitabine in guidelines, and the discordance between central and local reading of relapse became a design lesson for later adjuvant trials.