Improved survival with adding-on strategy after failure of nanoliposomal irinotecan plus 5-fluorouracil and leucovorin in metastatic pancreatic adenocarcinoma.

Background: Nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (FL) is indicated after progression on gemcitabine-based therapy in patients with metastatic pancreatic ductal adenocarcinoma (PDAC). However, salvage therapy after nal-IRI/FL failure remains to be established.

Methods: This study included 260 consecutive patients who initiated nal-IRI/FL therapy reimbursed by the National Health Insurance of Taiwan between January 2019 and March 2023. All patients were stratified into three groups (adding-on, regimen-shifting, and supportive) according to their strategy for nal-IRI/FL treatment. The prognostic factors were identified using univariate and multivariate analyses. Propensity score matching (PSM) was used to compare the median overall survival (OS) between the adding-on oxaliplatin or nab-paclitaxel and regimen-shifting groups following treatment failure with nal-IRI/FL.

Results: The median OS after the initiation of nal-IRI/FL was 7.8 (95% confidence interval [CI], 5.2-10.5) months and 6.1 (95% CI, 5.3-6.9) months for the adding-on oxaliplatin or nab-paclitaxel and regimen-shifting groups, respectively (P = 0.035). An Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1, no peritoneal metastasis before nal-IRI/FL, and the addition of oxaliplatin or nab-paclitaxel were significant independent prognostic factors for OS after nal-IRI/FL initiation. After PSM, the median OS after adding-on oxaliplatin/nab-paclitaxel or shifting regimens following the treatment failure of nal-IRI/FL were 4.1 (95% CI, 3.5-4.7) months and 3.1 (95% CI, 1.7-4.5) months, respectively (P = 0.039).

Conclusions: Addition of oxaliplatin or nab-paclitaxel to nal-IRI/FL was significantly associated with a better OS than regimen shifting after progression on nal-IRI/FL in patients with metastatic PDAC.