Reni M, et al. - In the PACT-19 trial, researchers investigated the activity of a novel four-drug regimen, comprising cisplatin, nab-paclitaxel, capecitabine, and gemcitabine (PAXG) compared with nab-paclitaxel plus gemcitabine in metastatic pancreatic adenocarcinoma. Outcomes in this small sample size study favor the PAXG regimen, justifying further investigation in a phase 3 trial in patients with metastatic pancreatic ductal adenocarcinoma.

Methods

• At San Raffaele Hospital in Italy, researchers performed this single-center, randomized, open-label, phase 2 trial.
• Patients (aged 18–75 years) with pathologically confirmed stage IV pancreatic ductal adenocarcinoma who had received no previous chemotherapy and had Karnofsky performance status of at least 70 were included.
• Using computer-generated permutated block randomization (block size of four), they randomly assigned patients (1:1) stratified by baseline concentration of carbohydrate antigen 19-9 to PAXG (cisplatin 30 mg/m², nab-paclitaxel 150 mg/m², and gemcitabine 800 mg/m 2 on days 1 and 15 and oral capecitabine 1250 mg/m 2 on days 1–28 every 4 weeks), or nab-paclitaxel and gemcitabine alone (nab-paclitaxel 125 mg/m² and gemcitabine 1000 mg/m² on days 1, 8, and 15 every 4 weeks).
• The proportion of patients who were progression-free at 6 months, analyzed in the intention-to-treat population was the primary endpoint of this study.
• March 31, 2018 was the data cutoff date.
• All patients who received at least one dose of study treatment comprised the safety population.

Results

• Researchers performed random assignment of 83 patients to treatment between April 22, 2014 and May 30, 2016, allocating 42 patients to PAXG and 41 patients to nab-paclitaxel plus gemcitabine.
• At 6 months, the PAXG group had 31 (74%, 95% CI 58–86) of 42 patients alive and free from disease progression compared with 19 (46%, 31–63) of 41 patients in the nab-paclitaxel plus gemcitabine group.
• Neutropenia (12 [29%] of 42 in the PAXG group vs 14 [34%] of 41 in the nab-paclitaxel plus gemcitabine group), anemia (nine [21%] vs nine [22%]), and fatigue (seven [17%] vs seven [17%]) were the most frequently encountered grade 3 adverse events.
• Neutropenia (five [12%] in the PAXG group vs two [5%] in the nab-paclitaxel plus gemcitabine group) was the most common grade 4 adverse event encountered.
• The nab-paclitaxel plus gemcitabine group showed 2 (5%) treatment-related deaths in comparison to none reported in the PAXG group.