In a phase II trial reported in JAMA Oncology, Davendra P.S. Sohal, MD, MPH, and colleagues found that neither of two perioperative chemotherapy regimens was associated with improved overall survival in patients with resectable pancreatic ductal adenocarcinoma compared with historical rates in adjuvant trials in this setting.
Davendra P.S. Sohal, MD, MPH
Study Details
In the open-label, "pick-the-winner" trial, 147 patients with resectable disease on Intergroup criteria were enrolled from U.S. National Clinical Trials Network sites between 2015 and 2018. Patients were randomly assigned to receive either: modified (m) FOLFIRINOX consisting of oxaliplatin at 85 mg/m2, irinotecan at 180 mg/m2, and infusional fluorouracil at 2,400 mg/m2 every 2 weeks for a total of six neoadjuvant doses and six adjuvant doses; or weekly nab-paclitaxel at 125 mg/m2 and gemcitabine at 1,000 mg/m2 for 3 weeks on/1 week off for a total of nine neoadjuvant doses and nine adjuvant doses. On central radiology review, 43 patients (29%) were deemed ineligible due to disease beyond resectability criteria. Among the 102 eligible patients, 55 received mFOLFIRINOX and 47 received gemcitabine/nab-paclitaxel. The primary outcome measure was 2-year overall survival, with the observed 2-year survival in each group being compared with the null hypothesis of 40% using a log-rank test.
Overall Survival
In the mFOLFIRINOX vs nab-paclitaxel/gemcitabine groups, 84% vs 85% completed preoperative chemotherapy, 73% and 70% underwent resection, and 49% and 40% completed all treatment.
Overall survival rates at 2 years were not significantly higher than the a priori threshold of 40% in either group: rates were 47% (95% confidence interval [CI] =31%–61%, P = .15) in the mFOLFIRINOX group and 48% (95% CI = 31%–63%, P = .14) in the gemcitabine/nab-paclitaxel group, with median overall survival durations of 23.2 months (95% CI = 17.6–45.9 months) and 23.6 months (95% CI = 17.8–31.7 months). Statistical differences between treatment groups were not assessed due to failure of both groups to meet the 2-year overall survival threshold.
KEY POINTS
- Neither treatment group had improved overall survival vs the predefined threshold.
- Overall survival at 2 years was 47% in the mFOLFIRINOX group and 48% in the gemcitabine/nab-paclitaxel group.
Overall response rates were 9% vs 21% (P = .15). Among the 40 patients in the mFOLFIRINOX group and 33 in the gemcitabine/nab-paclitaxel group who underwent surgical resection, R0 resection was achieved in 85% vs 85% (P > .99), node-negative resection in 40% vs 45% (P = .81), pathologic complete response in 3% vs 10% (P = .32) and moderate response in 22% vs 30% (P = .59). Median disease-free survival after resection was 10.9 months vs 14.2 months (P = .86).
Adverse Events
As related by the investigators, rates of the most frequently observed grade 3 and 4 adverse events, including hematologic toxicities, fatigue, diarrhea, nausea, and neuropathy, were as expected. During neoadjuvant treatment, patients in the mFOLFIRINOX group had a lower rate of neutropenia (19% vs 27%) and a higher rate of diarrhea (11% vs 4%; neither difference was statistically significant). The most common grade 3 or 4 surgery-related adverse events were anemia (14% vs 3%) and anorexia (5% vs 0%). In the adjuvant setting, the mFOLFIRINOX group had a lower rate of neutropenia (0% vs 27%, P = .002) and a higher rate of neuropathy (16% vs 4%, P = .21).
The investigators concluded: “This phase II randomized clinical trial did not demonstrate improved overall survival with perioperative chemotherapy, compared with historical data from adjuvant trials in resectable pancreatic cancer. Two-year overall survival was 47% with mFOLFIRINOX and 48% with gemcitabine/nab-paclitaxel for all eligible patients starting treatment for resectable pancreatic ductal adenocarcinoma. The trial also demonstrated adequate safety and high resectability rates with perioperative chemotherapy, and challenges in quality control for resectability criteria.”
Dr. Sohal, of the Division of Hematology and Oncology, University of Cincinnati, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit jamanetwork.com.
