Subgroup analysis by prior non-liposomal irinotecan therapy in NAPOLI-1: A phase 3 study of nal-IRI +/- 5-fluorouracil/leucovorin in patients with metastatic pancreatic ductal adenocarcinoma previously treated with gemcitabine-based therapy

[[abstract]]Introduction: In the global, randomized phase 3 NAPOLI-1 study, liposomal irinotecan (nal-IRI) + 5-fluorouracil/leucovorin (5-FU/LV) significantly increased median OS vs. 5-FU/LV by 45% (6.1 vs. 4.2 mo; unstratified HR = 0.67 [0.49–0.92]; p=.012) in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) who have progressed following gemcitabine-based therapy. Here, we present a subgroup analysis by prior non-liposomal irinotecan (NLI). Methods: Study methodology has been published (Wang-Gillam; Lancet 2016). Robustness of overall treatment effect was assessed by prospectively-defined subgroups, including prior NLI, based on primary survival analysis data (cut-off February 2014) of the ITT population.Results: OS, PFS and CA19-9 response rates in pts with (n¼29) and without (n¼207) prior NLI are shown (see Table). In pts without prior NLI, nal-IRIþ5-FU/LV (n¼105) improved median OS vs. 5-FU/LV (n¼102) by 2.5 mo to 6.7 mo (HR¼0.62; p<.01). Most frequent TEAEs were GI disorders (diarrhea, vomiting, nausea), regardless of prior NLI. ≧Grade 3 TEAEs and TEAEs leading to dose modification were similar in pts with (9 [75%]; 6 [50%]) and without (81 [77%]; 77 [73%]) prior NLI in the nalIRIþ5-FU/LV arm. Conclusion: This post-hoc subgroup analysis shows significant increases for nalIRIþ5-FU/LV vs. 5-FU/LV in OS, PFS and CA19-9 response rates in pts without prior NLI. Outcomes were similar in both arms in pts with prior NLI. The low number ofpts with prior NLI preclude firm conclusions from being drawn and further research is needed to explore the impact ofprior NLI