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Pancreatic ductal adenocarcinoma (PDA) is a relatively uncommon but lethal malignancy; when diagnosed at an advanced stage, the 5-year survival rate is 2% (1). Unfortunately, the majority of PDA patients are diagnosed at an advanced stage, where the median overall survival (OS) is only 4.6 months (2). Gemcitabine-based chemotherapy regimens have been the longstanding, first-line treatment option for locally advanced or metastatic PDA (3-5). Both gemcitabine plus nab-paclitaxel and FOLFIRINOX [5-fluorouracil/leucovorin (5-FU/LV) + irinotecan + oxaliplatin] have shown clear survival benefit and gained acceptance as frontline therapy for otherwise fit patients (6,7). Until the recent past, we were without proven secondline treatment options for patients who progressed on firstline gemcitabine-based regimens. In 2015, based upon the results of the phase 3 NAPOLI-1 trial (NCT01494506) (8), the nanoliposomal irinotecan (nal-IRI) plus 5-FU/LV regimen was approved for advanced PDA patients after failure of gemcitabine-based chemotherapy. Recently, Mercadé et al. (9) reported subgroup analyses of the NAPOLI-1 trial that investigated the patient, tumor, and prior treatment characteristics and their effects on survival outcomes. NAPOLI-1 was a global, phase 3, randomized, openlabel trial at 76 sites in 14 countries. In this trial, 417 patients with metastatic PDA who were previously treated with gemcitabine-based chemotherapy were randomly assigned (1:1:1) to three treatment arms: nal-IRI (80 mg/m) plus 5-FU/LV (400 mg/m of LV and 2,400 mg/m of 5-FU over 46 hours) every two weeks, nal-IRI monotherapy (120 mg/m2) every three weeks or 5-FU/LV monotherapy (200 mg/m of LV followed by 2,000 mg/m of 5-FU over 24 hours) in a four weeks on, two weeks off schedule. Patients receiving combination treatment with nal-IRI+5FU/LV demonstrated a significantly longer median OS compared with the 5-FU/LV cohort [6.1 vs. 4.2 months (HR: 0.67, 95% CI: 0·.49–0.92; P=0.012)] (8). Also, median progression-free survival (PFS) was significantly longer in the nal-IRI+5-FU/LV cohort compared to the 5-FU/LV cohort (3.1 vs. 1.5 months; HR 0.56; P=0.0001). Median OS (4.9 vs. 4.2 months; P=0.94) and PFS (2.7 vs. 1.6 months; P=0.1) were not significantly different between patients in the nal-IRI monotherapy group and those in the 5-FU/ LV monotherapy group. Objective response rates (ORR) were superior in the nal-IRI+5-FU/LV cohort compared with those in the 5-FU/LV cohort (16% vs. 1%; P<0.0001). The grade 3 or 4 adverse events (AEs) that occurred most frequently in the nal-IRI+5-FU/LV cohort were neutropenia, diarrhea, vomiting, and fatigue. Although AEs observed were higher in patients receiving nal-IRI+5-FU/ LV, the quality of life was not significantly different from patients in the 5-FU/LV cohort. The NAPOLI-1 clinical trial showed a 45% increase Editorial Commentary

Further defining the role of nanoliposomal irinotecan in pancreatic cancer