As reported in the Journal of Clinical Oncology by De La Fouchardière et al, the French phase III GEMPAX trial showed no overall survival benefit with second-line gemcitabine/paclitaxel vs gemcitabine alone after FOLFIRINOX (fluorouracil, oxaliplatin, and irinotecan) in patients with metastatic pancreatic ductal adenocarcinoma.
Study Details
In the multicenter open-label trial, 211 patients who had received prior FOLFIRINOX were randomly assigned 2:1 between June 2019 and March 2021 to receive gemcitabine at 1,000 mg/m2 and paclitaxel at 80 mg/m2 on days 1, 8, and 15 (n =140) or gemcitabine alone on days 1, 8, and 15 every 28 days; treatment was continued until disease progression or unacceptable toxicity. The primary endpoint was overall survival.
Overall Survival
Median follow-up for surviving patients was 13.4 months in the gemcitabine/paclitaxel group and 13.8 months in the gemcitabine group. Median overall survival was 6.4 months (95% confidence interval [CI] = 5.2–7.4 months) in the gemcitabine/paclitaxel group vs 5.9 months (95% CI = 4.6–6.9 months) in the gemcitabine group (hazard ratio [HR] = 0.87, 95% CI = 0.63–1.20, P = .4095).
KEY POINTS
- Gemcitabine/paclitaxel did not improve overall survival vs gemcitabine alone.
- The combination was associated with improved progression-free survival.
Objective response rates were 17.1% vs 4.2% (P = .008). Median progression-free survival was 3.1 months (95% CI = 2.2–4.3 months) vs 2.0 months (95% CI = 1.9–2.3 months), with a hazard ratio of 0.64 (95% CI = 0.47–0.89, P = .0067). Third-line treatment was received by 32.1% of patients in the gemcitabine/paclitaxel group and 46.5% of the gemcitabine group, including taxanes (2.1% vs 22.5%), platinum agents (9.3% vs 9.9%), and irinotecan (8.6% vs 1.4%).
Adverse Events
Treatment-related grade ≥ 3 adverse events occurred in 58.0% of patients in the gemcitabine/paclitaxel group vs 21.7% of the gemcitabine group, most commonly thrombocytopenia (19.6% vs 4.3%), neutropenia (15.9% vs 15.7%), anemia (15.2% vs 4.3%), neuropathy (12.3% vs 0%), and asthenia (10.1% vs 2.9%). Adverse events of any cause resulted in discontinuation of treatment in 16.7% vs 2.9% of patients. One treatment-related death occurred in the combination group, due to acute respiratory distress.
The investigators concluded. “While GEMPAX did not meet the primary endpoint of overall survival vs gemcitabine alone in patients with metastatic pancreatic ductal adenocarcinoma in the second-line setting, both progression-free survival and objective response rate were significantly improved.”
Christelle De La Fouchardière, MD, of the Medical Oncology Department, Institut Paoli-Calmettes, Marseille, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Institut National du Cancer. For full disclosures of the study authors, visit ascopubs.org.
