Liposomal Irinotecan Added to FOLFOX Promising First-Line Therapy for Metastatic Pancreatic Cancer

Barcelona, Spain—Liposomal irinotecan plus 5-fluorouracil/leucovorin and oxaliplatin (NAPOX) appears to be manageable, with promising antitumor activity for the first-line treatment of metastatic pancreatic cancer, according to data from a phase 1/2 trial presented at the ESMO 21st World Congress on Gastrointestinal Cancer.

“Previous studies have shown that there is an approximately 5-fold increase of drug in the tumors compared to the plasma suggesting local metabolism of the acting drug irinotecan,” stated Zev Wainberg, MD, Ronald Reagan UCLA Medical Center, Santa Monica, California, during his presentation.

The primary end points of the phase 1/2, open-label trial were to assess the safety, tolerability, and dose-limiting toxicities of NAPOX in patients with metastatic pancreatic cancer to determine appropriate dosing for the phase 3 trial. The secondary end points were measures of efficacy and toxicity.

The recommended dose of liposomal irinotecan 50 mg/m2 (free-base equivalent; FBE), oxaliplatin 60 mg/m2, leucovorin 400 mg/m2, 5-fluorouracil 2400 mg/m2 on days 1 and 15 of each 28-day cycle was selected for dose expansion (expansion phase) following 4 dose exploration cohorts (exploration phase).

A total of 56 patients were enrolled and treated in both phases of the trial, 32 of whom were treated with the recommended dose of NAPOX and moved forward in the trial.

Overall, 9 dose-limiting toxicities were reported by 5 patients in the exploration phase of the trial: diarrhea (n = 2), vomiting (n = 1), anal fissure (n = 1), anal inflammation (n = 1), proctalgia (n = 1), neutropenic infection (n = 1), neutropenic sepsis (n = 1), and febrile neutropenia (n = 1).

Treatment-related adverse events grade ≥3 were reported by 29 patients, including neutropenia (n = 9), febrile neutropenia (n = 4), hypokalemia, (n = 4), diarrhea (n = 3), nausea (n = 3), anemia (n = 2), and vomiting (n = 2).

Serious adverse events were reported by 31 patients, 23 of which were deemed treatment-related. Treatment-related adverse events leading to discontinuation were reported in 15 patients, and dose adjustments due to adverse events were required in 36 patients.

Disease control was achieved in 23 (71.9%) of the 32 patients who received the recommended dose of NAPOX at 16 weeks. The best overall response was a complete response in 1 patient, partial response in 10 patients, and stable disease in 15 patients, with an overall response rate of 34%. At data cut-off, 15 of the 32 patients were still receiving therapy.

“The safety profile of this regimen, which is now known as NAPOX, was manageable for the first-line treatment of metastatic cancer,” concluded Dr Wainberg.

“Promising anti-tumor activity was identified and the data for overall survival and progression-free survival are not yet mature because as of the data cut, virtually 50% of the patients enrolled on the study remained on treatment,” he added.—Janelle Bradley

Wainberg Z, Boland P, Lieu C, et al. A phase 1/2, open-label, dose-expansion study of liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) and oxaliplatin (OX) in patients with previously untreated metastatic pancreatic cancer. Presented at: the ESMO 21st World Congress on Gastrointestinal Cancer; July 2019; Barcelona, Spain. Abstract SO-005.