A recent study performed a systematic review and network meta-analysis of previously gathered clinical trial data to compare the standard of care for advanced pancreatic ductal adenocarcinoma (PDAC), currently first-line chemotherapy, with other treatment options for PDAC. The review specifically targeted research highlighting the efficacy and toxicity of various treatment options.
A team of researchers from Italy conducted the review “due to the absence of head-to-head comparisons in clinical trials.” To gather data, the authors searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, and oncological meetings websites. The data search concluded on November 15, 2023.
Summary data from phase II and III randomized controlled trials published following January 1, 2000, were assessed. The investigators evaluated progression-free survival (PFS) and overall survival (OS) as the primary endpoints, specifically targeting data on “first-line treatments in patients with previously untreated, unresectable, locally advanced or metastatic PDAC.”
Several criteria models were used to review the selected data. The researchers selected a fixed-effect model using deviance information criterion and “hazard ratios (HR) with 95% credible intervals were estimated using a Bayesian approach.” The Cochrane Risk of Bias 2 (RoB 2) tool was used to assess “the risk of bias,” and to grade the selected studies as “low, some concerns, or high risk of bias.” The quality of evidence within the studies was evaluated with the “Grading of Recommendations Assessment, Development, and Evaluation approach.”
In the analysis, the investigators combed through 6,050 records comprising 79 randomized controlled trials and 22,168 patients. Gemcitabine was the “most frequent comparator,” appearing in 63% of trials, and was the reference treatment.
According to the systematic review, the most effective treatments for PFS were “gemcitabine plus nab-paclitaxel alternating folinic acid, fluorouracil, and oxaliplatin ([FOLFOX] HR 0.32, 95% credible interval 0.22-0.47), cisplatin, nab-paclitaxel, capecitabine, and gemcitabine ([PAXG] 0.35, 0.22-0.55), and liposomal irinotecan in combination with fluorouracil, leucovorin, and oxaliplatin ([NALIRIFOX] 0.43, 0.34-0.54), followed by fluorouracil, leucovorin, irinotecan, and oxaliplatin ([FOLFIRINOX] 0.55, 0.47-0.65) and gemcitabine plus nab-paclitaxel (0.62, 0.54-0.72).”
The review found that the most effective treatment for OS was “PAXG (HR 0.40. 95% credible interval 0.25-0.65), gemcitabine plus nab-paclitaxel alternating FOLFOX (0.46, 0.32-0.66), and NALIRIFOX (0.56, 0.45-0.70).” The treatment with the next highest benefit was “FOLFIRINOX (0.66, 0.56-0.78) and gemcitabine plus nab-paclitaxel (0.67, 0.59-0.77).” Overall, the risk of bias was measured as “low to some concerns.”
In their interpretation of the findings, the researchers stated that “NALIRIFOX and FOLFIRINOX should be the preferred options for patients who can tolerate these regimens.” The combination of gemcitabine plus nab-paclitaxel was listed as a “viable alternative,” especially for patients who are unable to receive triplet therapy.
Source: The Lancet Oncology
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