Gemcitabine-resistant pancreatic cancer: a second-line option

1report on a randomised phase 3 trial (NAPOLI-1) in 417 patients with metastatic gemcitabine-resistant pancreatic cancer. The primary endpoint of overall survival was improved signifi cantly with the combination of nanoliposomal irinotecan plus fl uorouracil and folinic acid when compared with a control of fl uorouracil and folinic acid (6·1 months [95% CI 4·8–8·9] vs 4·2 months [3·3–5·3]; hazard ratio [HR] 0·67, 95% CI 0·49–0·92). Subgroup analyses consistently favoured the combination treatment, further supporting a robust treatment eff ect on overall survival. NAPOLI-1 is one of two phase 3 trials to be done in the second-line gemcitabine-resistant setting, the other study being CONKO-003. 2 In that trial, second-line oxaliplatin plus fl uorouracil and folinic acid was assessed with fl uorouracil and folinic acid alone, and the primary endpoint of overall survival was also met. Metastatic pancreatic cancer has a dismal prognosis, with median survival of 4–6 months, and is associated with substantial morbidity. 3,4 Because of its particular biology, pancreatic cancer is notoriously resistant to many types of chemotherapy. As a result, few treatment options currently exist for patients who have progressed on fi rst-line gemcitabine-based therapy and are willing and able to undergo further chemotherapy. Hence, a confi rmed survival benefi t in this population of patients with an unmet clinical need is especially exciting. Expanded analyses of NAPOLI-1 in the per-protocol population have further confi rmed the favourable eff ects of nanoliposomal irinotecan plus fl uorouracil and folinic acid on overall survival, compared with fl uorouracil and folinic acid. 5 In patients who received an 80% or