In a phase III trial (TRYBECA-1) reported in the Journal of Clinical Oncology, Hammel et al found that the addition of eryaspase (suspension of erythrocytes encapsulating L-asparaginase) to chemotherapy did not significantly improve outcomes in second-line treatment of patients with advanced pancreatic ductal adenocarcinoma (PDAC).
Study Details
In the international open-label trial, 512 patients were randomly assigned between September 2018 and December 2020 to receive eryaspase plus chemotherapy (n = 255) or chemotherapy alone (n = 257). Treatment was administered in 4-week cycles and consisted of eryaspase at 100 U/kg on days 1 and 15; and investigator's choice of chemotherapy consisting of either gemcitabine at 1,000 mg/m2 and nab-paclitaxel at 125 mg/m2 on days 1, 8, and 15 or irinotecan at 180 mg/m2 (or nanoliposomal irinotecan at 70 mg/m2) on days 1 and 15, 5-fluorouracil at 2,400 mg/m2 as one 46-hour infusion (with a bolus of 400 mg/m2), and leucovorin at 400 mg/m2 on days 1 and 15. Treatment continued until disease progression or unacceptable toxicity. The primary endpoint was overall survival.
Key Findings
Median overall survival was 7.5 months (95% confidence interval [CI] = 6.5–8.3 months) in the eryaspase group vs 6.7 months (95% CI = 5.4–7.5 months) in the control group (hazard ratio [HR] = 0.92, 95% CI = 0.76–1.11, P = .374).
Median progression-free survival was 3.7 months (95% CI = 3.4–4.1 months) in the eryaspase group vs 3.4 months (95% CI = 2.0–3.7 months) in the control group (HR = 0.88, 95% CI = 0.73–1.07, P = .196); the use of subsequent therapies was similar in the two groups. Objective response rates were 16.1% vs 12.5% (odds ratio = 1.35, 95% CI = 0.81–2.24).
In both the eryaspase group and the control group, the most common adverse events of any grade were asthenia (75.4% vs 70.7%), diarrhea (55.6% vs 45.5%), and anemia (51.6% vs 40.7%). The most common grade 3 or 4 adverse events were neutropenia (25.4% vs 20.3%), asthenia (16.9% vs 13.8%), and anemia (17.3% vs 12.2%). Treatment-related death occurred in four patients (1.6%) vs two patients (0.8%).
The investigators concluded: “The addition of eryaspase to chemotherapy did not improve [overall survival, progression-free survival, or objective response rate]. [Adverse events] were generally consistent with previous reports of chemotherapy. These results do not support additional development of eryaspase in [pancreatic cancer].”
Pascal Hammel, MD, of Hȏpital Paul Brousse, Villejuif, France, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Erytech Pharma. For full disclosures of all study authors, visit ascopubs.org.
