Eryaspase May Provide Second-Line Option in Pancreatic Cancer

Pascal Hammel, MD, PhD

An unmet need exists in the second-line treatment of patients with pancreatic adenocarcinoma, explained Pascal Hammel, MD, PhD. To address this, clinical trials are focusing on this setting, such as the TRYbeCA-1 study (NCT03665441) of the L-asparaginase-based therapy eryaspase (Graspa).

The TRYbeCA-1 study is investigating the addition of eryaspase to chemotherapy compared with chemotherapy alone in this population. This trial may provide a new option for patients who progress on first-line treatment, according to Hammel, who is the principal investigator of the study.

OncLive: Could you provide some background on the data seen with eryaspase?

In an interview with OncLive, Hammel, a gastroenterologist, oncologist, Hôpital Beaujon, Clichy France, discussed the potential for eryaspase, and the future direction of the pancreatic cancer landscape.Hammel: In 2017, we presented the [phase IIb] results of the TRYbeCA-1 study testing eryaspase in patients with pancreatic cancer in the second line following progression on FOLFIRINOX or gemcitabine/nab-paclitaxel (Abraxane)-based chemotherapy. The treatment was well supported. Patients were selected, as only about 50% of patients with pancreatic cancer are able to receive second-line therapy after tumor progression. Both progression-free and overall survival was significantly increased in this phase II trial. We hypothesized that having low asparaginase center activity was predictive of good activity, but that was not the case. Even the group with high asparaginase center activity had good tumor control using eryaspase.

If these findings are positive, what impact could the inclusion of this agent have on the landscape?

Is there anything else going on in pancreatic cancer that you would like to mention?

This was a strong signal to go onto a phase III study with a larger number of patients. In this study, we will include 480 patients from the United States and Europe to see if our feeling about the activity of this drug is confirmed in a phase III setting. We plan to show a difference with a hazard ratio of 0.72. Patients in arm A will receive either an irinotecan-based therapy (FOLFIRI or Onivyde/5-FU/leucovorin) or gemcitabine and nab-paclitaxel, with or without eryaspase. Arm B will receive irinotecan-based therapy or gemcitabine and nab-paclitaxel. All patients on this trial are eligible to receive second-line therapy.This study is a very important one because the second-line treatment of pancreatic cancer with chemotherapy is really an unmet need. There are so few drugs, and a lot of patients. We are not sure which new drugs will win, but there is a big hope to do something with eryaspase. With the tolerance and mechanism of the drug, which is a more metabolic treatment, I have hope that we can show something and learn something about the drug. It is very important to not miss the possibility to include patients on this study. It is on 2 continents and will run pretty fast. To my knowledge, there are not many concurrent studies. The time to do it is now. It is very important for our patients.I have been working in pancreatic cancer for a very long time. All options are very interesting for first- and second-line treatment, as well as trends in genetics and screening of patients at risk. There is a lot to do before we find anything. Also, we must support the patient. Not only chemotherapy, radiation, or surgery, but also support such as physical activity, nutrition, and psychological aspects. To treat [patients with] pancreatic cancer, you must have a whole team around the patient.

There is a growing incidence of pancreatic cancer, but you cannot check everyone for it. We are trying to detect more populations of interest. For example, people with several cases of pancreatic cancer in their family or those with genetic syndromes with high incidences for pancreatic cancer.

When I was younger, I said that pancreatic cancer was like Mount Everest: To climb to the top is difficult. There is not one [type of] pancreatic cancer, so we should say all pancreatic cancers, as in plural. There are very different genetic pathways¬; the way these diseases progress or remain stable, respond to treatment, or relapse after surgery is very different. We have to put a lot of effort into the patient populations with pancreatic cancer at big centers, and give the best treatment first. Best supportive care is not just palliative treatment for the end of life, it starts at the very beginning of each treatment for each patient with pancreatic cancer.