Selected subgroup analyses of liposomal irinotecan (nal-IRI) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) in the global NAPOLI-1 phase III trial
Authors: T. Macarulla Mercadé, K. Lee, G. Lakatos, A. Wang-Gillam, L. Chen, B. Mirakhur, F. De Jong
Journal: Annals of Oncology (2018)

Introduction: NAPOLI1 (NCT01494506; Wang-Gillam et al., Lancet 2016;387:545-57) was a global phase 3 study of patients with mPDAC who progressed following gemcitabine-based therapy. In patients receiving nalIRI+5FU/LV, median overall survival (mOS) was significantly higher (6.1 months) compared with 5FU/LV (4.2 months; unstratified HR = 0.67; P = 0.012). Here, we summarise four separate NAPOLI-1 subgroup analyses investigating the effect of selected baseline parameters. Methods: These post-hoc analyses explored outcomes in patients with or without metabolism and nutrition disorders (including hypercholesterolemia and decreased appetite, comprising anorexia, poor appetite, lack of appetite and loss of appetite; abstract_#327), by primary tumour location (pancreatic head only, body only, tail only, and multiple locations including or excluding the head; abstract_#335), with or without a biliary stent (abstract_#338), and by best response to prior therapy (complete response/partial response [CR/PR] vs not-CR/PR, and CR/PR/stable disease [CR/PR/SD] vs not-CR/PR/SD; abstract_#339). Results: For ITT patients in the metabolism and nutrition disorders analysis (abstract_#327), survival was significantly reduced in those patients (n = 77) with baseline decreased appetite compared with patients (n = 340) without decreased appetite (mOS: 3.6 vs 5.3 months; HR = 1.65; P < 0.001). A trend for lower survival was observed in patients with hypercholesterolemia. In the analysis investigating the effect of primary tumour location on outcomes (abstract_#335), survival was comparable across primary tumour location subgroups (HRs=0.87–1.06). However, patients receiving nal-IRI+5-FU/LV showed an increased survival across primary tumour location subgroups compared with 5-FU/LV (HRs=0.39–0.88 for groups n > 10 per arm). In ITT patients with a biliary stent at baseline (n = 37), survival was comparable to those without a stent (mOS: 5.3 vs 4.8 months; HR = 0.97) (abstract_#338). In patients with a stent and receiving nal-IRI+5-FU/LV (n = 15), we observed a trend for increased survival compared with patients receiving 5-FU/LV (mOS: 6.2 vs 5.2 months; HR = 0.44; n = 8). In patients without a stent, a similar survival benefit was seen for nal-IRI+5-FU/LV (n = 102) versus 5-FU/LV (n = 111) (mOS: 6.1 vs 4.2 months; HR = 0.68). For subgroups stratified by response to prior therapy (abstract_#339), there was a trend for increased survival in patients with CR/PR compared with not-CR/PR (mOS: 5.6 vs 4.8 months; HR = 0.73). In patients with CR/PR/SD survival was similar compared with not-CR/PR/SD (mOS both 4.9 months, HR = 0.95). A trend for increased survival was also shown in patients receiving nal-IRI+5-FU/LV with CR/PR (n = 11) compared with not-CR/PR (n = 106) (mOS: 9.3 vs 6.1 months; HR = 0.64). Survival was comparable in patients with CR/PR/SD (n = 58) vs not-CR/PR/SD (n = 59) (mOS: 6.2 vs 6.1 months; HR = 1.04). Drug related AEs and dose modifications/discontinuations in the different subgroups were generally comparable to the NAPOLI-1 study. Conclusion: In the NAPOLI-1 study, decreased appetite at baseline was shown to be prognostic for survival in patients with mPDAC who progressed after gemcitabine-based therapy. These results indicate that appropriate management is essential in patients with decreased appetite. We did not identify a significant prognostic effect of primary tumour location, biliary stent, or best response to prior therapy in either the NAPOLI-1 ITT population or the nal-IRI+5-FU/LV treatment arm on survival after trial inclusion. Nonetheless, a consistent treatment benefit was observed in patients treated with nal-IRI+5-FU/LV vs 5-FU/LV alone across subgroups.