Eryaspase regimen safe, may benefit certain patients with advanced pancreatic cancer
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A study of eryaspase added to chemotherapy did not meet its primary endpoint of improved OS among patients with advanced pancreatic cancer, according to a presentation at ASCO Gastrointestinal Cancers Symposium.
However, the second-line combination therapy had a manageable safety profile and provided an encouraging survival benefit among a subgroup of patients who received a fluoropyrimidine- and irinotecan-based chemotherapy regimen, results of the randomized phase 3 Trybeca-1 study showed.
“All efficacy indicators showed a trend toward improved outcome for the chemotherapy-plus-eryaspase arm vs. chemotherapy alone,” Pascal Hammel, MD, PhD, professor and gastroenterologist oncologist at Beaujon Hospital in Clichy, France, said during the presentation.
Background
Eryaspase (Graspa, Erytech Pharma), which consists of L-asparaginase encapsulated inside donor-derived red blood cells, induces the degradation of asparagine and glutamine, crucial for growth and survival of cancer cells, researchers wrote. In a prior, phase 2 study, eryspase plus chemotherapy showed an improvement in OS and PFS among patients with advanced pancreatic cancer.
“Eryaspase is an ASNase within red blood cells, thereby prolonging the activity and reducing the toxicity of the free enzyme,” Hammel said. “This drug has shown to be well-tolerated and a potential effective chemotherapy partner for patients with pancreatic cancer.”
Methodology
The current study’s analyses included 512 patients with advanced pancreatic adenocarcinoma who had progressed on only one prior line of systemic anticancer therapy. Researchers randomly assigned patients 1:1 to receive gemcitabine/nab-paclitaxel or irinotecan/5-FU therapy (depending on first-line treatment) with or without eryaspase, administered via IV infusion on day 1 and day 15 of each 4-week cycle.
OS served as the primary endpoint.
Key findings
Results showed the study failed to meet the primary endpoint of OS (HR = 0.92; 95% CI, 0.76-1.11).
Researchers reported median OS of 7.5 months (95% CI, 6.5-8.3) for patients treated with eryaspase plus chemotherapy compared with 6.7 months (95% CI, 5.4-7.5) for chemotherapy alone, and median PFS of 3.7 months vs. 3.5 months (HR = 0.89; 95% CI, 0.73-1.07).
They observed a trend of nominal OS benefit among 107 patients treated with eryaspase and irinotecan/5-FU compared with 109 patients in the control subgroup (median OS, 8 months vs. 5.7 months; HR = 0.81; 95% CI, 0.6-1.09). Additionally, they noted a consistent treatment effect across subgroups of patients with various prognostic factors.
Eryaspase did not appear to enhance toxicity of chemotherapy, Hammel said. He reported disease control rates of 57.6% in the eryaspase group and 49% in the control group. The most common grade 3 or grade 4 adverse events in the eryaspase group included asthenia (16.9%), diarrhea (7.6%) and anemia (17.3%).
Implications
Although the trial did not meet its primary endpoint, Hammel noted the positive trend, warranting further study.
“There was a trend toward improved OS in patients who received eryaspase and fluoropyrimidine/irinotecan therapy compared with the control arm,” Hammel said. “The treatment effect was very consistent and stable across all subgroups.”
Perspective
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Vincent Chung, MD
Pancreatic cancer is a deadly disease, and by 2030 it will be the second-leading cause of cancer-related death. Novel therapies for refractory cancer are urgently needed to improve OS.
The NAPOLI-1 trial showed an improvement in median OS of 6.1 months with the combination of liposomal irinotecan and 5-FU. The well-conducted Trybeca-1 trial evaluated standard chemotherapy with or without eryaspase.
Eryaspase is an encapsulated L-asparaginase in red blood cells designed to target cancer cells due to its altered amino acid metabolism that requires asparagine for cell survival. In the phase 2 study of eryaspase in combination with gemcitabine or FOLFOX, the combination demonstrated an impressive hazard ratio of 0.62 for OS. The phase 3 clinical trial used different chemotherapy backbone regimens.
The study did not meet its primary endpoint, but there appeared to be an improvement in survival for the FOLFIRI group.
At this time, it is unknown if there is a synergy with 5-FU-based chemotherapy regimens or if the additive effect is only with more inferior chemotherapy regimens as compared with gemcitabine plus nab-paclitaxel. Additional work needs to be done to evaluate the synergy with the chemotherapy treatments.
Reference:
Wang-Gillam A, et al. Lancet. 2016;doi:10.1016/S0140-6736(15)00986-1.
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Hammel P, et al. Abstract 518. Presented at: ASCO Gastrointestinal Cancers Symposium Jan. 20-22, 2022; San Francisco.
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