NALIRIFOX versus nab-paclitaxel and gemcitabine in older patients with treatment-naive metastatic pancreatic cancer: a subgroup analysis of the pivotal NAPOLI 3 trial

BACKGROUND: The phase III NAPOLI 3 trial established liposomal irinotecan in combination with 5-fluorouracil/leucovorin plus oxaliplatin (NALIRIFOX) as a superior first-line (1L) treatment option compared with gemcitabine plus nab-paclitaxel (Gem + NabP) in patients with previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC), without imposing an upper age limit on enrollment. The current analysis of the NAPOLI 3 data investigated the potential impact of older age on the efficacy and safety of NALIRIFOX. PATIENTS AND METHODS: Adults with previously untreated mPDAC were randomly assigned in a 1 : 1 ratio to receive NALIRIFOX or Gem + NabP. This post hoc analysis compared outcomes for patients aged ≥70 years versus <70 years. Endpoints included overall survival (OS), progression-free survival (PFS), and safety. No statistical comparison was carried out. RESULTS: Of the 770 patients in the NAPOLI 3 population, 553 were aged <70 years and 217 were aged ≥70 years. Median OS and median PFS with NALIRIFOX were 11.7 months and 7.4 months, respectively, in the <70 years subgroup (n = 275) and 10.0 months and 7.3 months, respectively, in the ≥70 years subgroup (n = 108). The benefit of NALIRIFOX versus Gem + NabP was preserved in the older versus younger subgroup. There was no evidence of increased treatment-related toxicity in the older (versus younger) subgroup. CONCLUSIONS: NALIRIFOX improved mPDAC survival versus Gem + NabP irrespective of patient age, with no signals for reduced tolerability in the older (versus younger) patients. The results provide reassurance that triplet therapy with NALIRIFOX is an efficacious and tolerable regimen in older treatment-naive patients with mPDAC who were fit enough for inclusion in NAPOLI 3, supporting consideration of its use as 1L therapy in this population.