medwireNews: The PAXG regimen comprising cisplatin, nab-paclitaxel, capecitabine, and gemcitabine shows promising efficacy and tolerability relative to the standard combination of nab-paclitaxel plus gemcitabine in chemotherapy-naïve patients with metastatic pancreatic ductal adenocarcinoma (PDAC), say the PACT-19 investigators.
The primary endpoint of progression-free survival (PFS) at 6 months was achieved by 74% of 42 patients with stage IV disease who were randomly allocated to the PAXG group, and received cisplatin 30 mg/m2, nab-paclitaxel 150 mg/m2, and gemcitabine 800 mg/m2 on days 1 and 15 of each 28-day cycle, plus capecitabine 1250 mg/m2 every day.
By contrast, the 6-month PFS rate was 46% among the 41 participants given nab-paclitaxel 125 mg/m2 alongside gemcitabine 1000 mg/m2 on days 1, 8, and 15 of every 28-day cycle.
The median PFS times for the PAXG and standard treatment groups were 8.3 and 6.1 months, respectively (hazard ratio [HR]=0.56), while the corresponding durations for median overall survival (OS) were 14.4 and 10.7 months (HR=0.60).
OS at the 1-year mark was 62% in the PAXG treatment arm, compared with 44% in the nab-paclitaxel plus gemcitabine arm, with 2-year rates of 24% and 12%, respectively. Michele Reni and colleagues, from the San Raffaele Scientific Institute in Milan, Italy, describe the rates achieved by PAXG-treated patients as “unusual” in the metastatic PDAC setting.
Moreover, the four-drug regimen had “acceptable tolerability and a toxicity profile that is similar to those of the current standards of treatment,” they write in The Lancet Gastroenterology & Hepatology.
Neutropenia was the most common severe adverse event, with grade 3 events occurring in 29% of patients who received PAXG and 34% of those given the standard regimen, and grade 4 events in a respective 12% and 5% of participants.
The next most frequent toxicities were grade 3 anemia and fatigue, with rates of 21% versus 22% and 17% versus 17% in the PAXG and standard treatment groups, respectively.
None of the deaths in the PAXG arm were attributed to treatment-related toxicity, but two patients in the nab-paclitaxel plus gemcitabine group died within 30 days of receiving chemotherapy.
“The identification of a safe and effective combination of drugs could not only be of use in patients who are not eligible for targeted therapy to increase their progression-free survival and overall survival, but could also be used as a robust backbone on which to build personalised treatment,” say the study authors.
And they conclude: “Despite the small sample size, our findings suggest that the PAXG regimen warrants further investigation in a phase 3 trial in patients with metastatic pancreatic ductal adenocarcinoma.”
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