Reduced-Dose Treatment is Effective Against Advanced Pancreatic Cancer

In a real-world study, dose reductions (DRs) of an FDA-approved therapy for pancreatic cancer were effective and associated with improved clinical outcomes in the treatment of advanced disease.

Liposomal irinotecan is an intravenous topoisomerase inhibitor that is approved in combination with fluorouracil and leucovorin for the treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC) after disease progression following gemcitabine therapy.

This retrospective study included a main cohort of 320 mPDAC patients who underwent liposomal irinotecan treatment at the indicated dose (70 ± 5 mg/m²). DRs occurred in 28.4% of patients. Endpoints included treatment duration, overall survival (OS), time to treatment discontinuation (TTD), and occurrence of adverse effects (AEs).

A validation cohort of 348 mPDAC patients who received at least three cycles of liposomal irinotecan was also included. Participants were divided according to initial dosage: 63% started at the indicated dose (70 mg/m²), while 37% started at a low dose (<65 mg/m²). DRs occurred in 31.3% of patients.

In the main cohort DRs were associated with a longer median OS compared with patients who received the indicated dose (7.7 months [95% confidence interval (CI) 6.2–10.2] vs 3.6 months [95% CI 3.2–4.1]). DRs were also associated with longer median continuous treatment duration (15.3 weeks vs 4.3 weeks for indicated dose), and longer median TTD (4.2 months [95% CI 3.0–4.9] vs 1.4 months [95% CI 1.0–1.5]).

Among patients starting at the indicated dosage in the validation cohort, DRs were also associated with a longer OS (8.9 months [95% CI 7.3–10.8] vs 6.0 months [95% CI 4.8–7.2]) and longer treatment duration (19.0 weeks vs 10.3 weeks) compared with those without DRs. For patients starting at the low dose, DRs were associated with a longer OS (7.7 months [95% CI 5.0–14.9] vs 6.0 months [95% CI 4.7–7.2]) and longer treatment duration (16.1 weeks vs 8.6 weeks).

A higher proportion of patients with DRs experienced grade 3 and/or 4 AEs. The association between DRs and clinical outcomes was independent of starting dose.

“A reduction in the dose of liposomal irinotecan did not result in a decrease in clinical effectiveness,” the researchers concluded. “Future prospective studies are required to characterize further the association between liposomal irinotecan dosing and clinical outcomes.”

This study was published in Future Medicine.