In an interim analysis of a Japanese phase II/III trial (GENERATE, JCOG1611) reported in the Journal of Clinical Oncology, Ohba et al compared the survival benefit of mFOLFIRINOX (modified fluorouracil, leucovorin, irinotecan, oxaliplatin) or S-IROX (S-1, irinotecan, oxaliplatin) vs nab-paclitaxel plus gemcitabine in first-line treatment of metastatic or recurrent pancreatic cancer.
Study Details
In the open-label multicenter trial, 527 patients were randomly assigned 1:1:1 between April 2019 and March 2023 to receive nab-paclitaxel plus gemcitabine (n = 176), mFOLFIRINOX (n = 175), or S-IROX (n = 176). Among them, 426 patients, consisting of 141 in the nab-paclitaxel plus gemcitabine group, 143 in the mFOLFIRINOX group, and 142 in the S-IROX group, were enrolled through September 2022 and included in the planned interim analysis.
Key Findings
Median overall survival was 14.0 months in the mFOLFIRINOX group (hazard ratio [HR] vs nab-paclitaxel plus gemcitabine group = 1.31, 95% confidence interval [CI] = 0.97–1.77) and 13.6 months in the S-IROX group (HR vs nab-paclitaxel plus gemcitabine group = 1.35, 95% CI = 1.00–1.82) compared with 17.1 months in the nab-paclitaxel plus gemcitabine group.
The probability of achieving overall survival superiority over the nab-paclitaxel plus gemcitabine group in the final analysis was found to be less than 1% for both the mFOLFIRINOX group and the S-IROX group. The trial was terminated due to futility.
Among all 527 patients, grade 3 or 4 neutropenia was more common in the nab-paclitaxel plus gemcitabine group (60.3%) vs the mFOLFIRINOX group (51.5%) and the S-IROX group (38.7%). Grade 3 or 4 anorexia and diarrhea were less common in the nab-paclitaxel plus gemcitabine group (5.2% and 1.1%) vs the mFOLFIRINOX group (22.8% and 8.8%) and the S-IROX group (27.6% and 23.0%). Treatment-related death occurred in one patient in the S-IROX group.
The investigators concluded: “Neither mFOLFIRINOX nor S-IROX appeared to be superior compared with nab-paclitaxel plus gemcitabine as the first-line treatment for metastatic or recurrent pancreatic cancer.”
Makoto Ueno, MD, of the Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Japan Agency for Medical Research and Development and National Cancer Center Research and Development Fund. For full disclosures of all study authors, visit ascopubs.org.
