Efficacy and safety of nanoliposomal irinotecan plus 5-fluorouracil and l-leucovorin in rare histological subtypes of pancreatic cancer.

BACKGROUND

Pancreatic cancers other than pancreatic ductal adenocarcinoma (PDAC) are rare and heterogeneous, accounting for fewer than 5%-7% of all pancreatic cancers. These include acinar cell carcinoma, undifferentiated carcinoma, adenosquamous carcinoma, colloid carcinoma, neuroendocrine carcinoma (NEC), mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN), and invasive intraductal papillary mucinous carcinoma (IPMC). Optimal treatment strategies, including sequencing and later-line options, remain unclear. Although nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil (5-FU) and l-leucovorin (LV) is effective in gemcitabine-refractory PDAC, its role in these rare subtypes is unknown.

METHODS

We retrospectively analyzed nine patients with one of these rare subtypes who received nal-IRI plus 5-FU and LV between June 2020 and November 2024. Efficacy and safety were evaluated.

RESULTS

The cohort included two cases each of IPMC and adenosquamous carcinoma, and one case each of colloid carcinoma, undifferentiated carcinoma, acinar cell carcinoma, NEC, and MiNEN. Partial responses were observed in four patients, including undifferentiated carcinoma, acinar cell carcinoma, NEC, and MiNEN, even among tumors refractory to gemcitabine- or platinum-based regimens. Disease control was achieved in seven patients (77.8%). The median progression-free survival was 6.8 months. Disease control exceeding 12 months was observed in three patients. Median overall survival from first-line therapy was not reached. Treatment-related toxicities were generally manageable, with neutropenia being the most common grade ≥ 3 adverse event.

CONCLUSION

Nal-IRI plus 5-FU and LV showed antitumor activity and was tolerable among the nine patients analyzed in this study, suggesting it may be a therapeutic option in second- or later-line settings for rare pancreatic cancer.