Elizabeth R. Cullen, MSN, ARNP, talks severe oral mucositis management for patients with locally advanced head and neck cancer.
Avasopasem (GC4419) decreased the incidence of severe oral mucositis (SOM) brought on by intensity-modulated radiotherapy (IMRT) and cisplatin in patients with locally advanced head and neck cancer, according to data from the phase 3 ROMAN trial (NCT03689712) presented by Elizabeth R. Cullen, MSN, ARNP, at the 48th Annual Oncology Nursing Society.
Patients receiving 60-72 Gy of IMRT plus cisplatin were given avasopasem, an investigative selective small molecule dismutase mimetic, at a dose of 90 mg 1 hour before each radiotherapy fraction. The incidence of SOM during IMRT was 54% in patients receiving avasopasem (n = 241) vs 64% among those who received placebo (n = 166) which was statistically significant (P = 0.045). The median duration of SOM throughout was 8 days vs 18 days, respectively, which was also statistically significant (P = 0.002).
Other end points demonstrated benefit with the treatment as well. The median onset time of SOM was delayed in the avasopasem arm (49 days) compared with the placebo arm (38 days), yielding a relative reduction of 28%, which statistically significant (P = .002). For patients who received 50 Gy of IMRT, the SOM incidence rate was 28% compared with 45%, respectively (P < .001). Lastly, there was also a 21% reduction in overall utilization of feeding tubes among patients receiving avasopasem, and a 13% reduction in the use of narcotics for oral mucositis pain.
Based on these findings, the agent is under priority review. The Prescription Drug User Fee Act (PDUFA) target date is August 9, 2023.
In an interview with Oncology Nursing News®, Cullen, a nurse practitioner in the Department of Radiation Oncology at the University of Iowa Hospitals and Clinics, unpacked the significance of these findings and explained how avasopasem could be leveraged to manage SOM if it is approved.
Oncology Nursing News: Please discuss the background of this study.
Cullen: The standard of care for locally advanced head and neck cancer is 7 weeks of IMRT therapy plus cisplatin chemotherapy. Approximately 70% of patients that go through this treatment course will develop SOM and severe is categorized as either a grade 3 or 4 event. With grade 3 [events], patients have oral ulcerations and are unable to eat solid foods; a grade 4 is [when patients have] oral mucosal ulcerations and are unable to eat liquid or a solid diet. Currently, there are no medications that are FDA approved that will mitigate the SOM.
There were 407 patients [that] participated in the study, they were randomized in a 3:2 ratio of avasopasem to placebo, and they received a 60-minute infusion Monday through Friday on the days of their radiation therapy. The patients that were included in the study were patients with oral cavity or oropharynx tumors, they had to have squamous cell pathology, and they had to be eligible to receive the 7 weeks of IMRT plus cisplatin.
What were the main findings?
The biggest finding was that the primary end point of the study was met and there was a statistically significant decrease in the incidence of SOM in patients with locally advanced head and neck cancer. Avasopasem mitigated the effects of cisplatin on the kidneys, and acute and chronic kidney disease was decreased in the avasopasem group vs placebo. Lastly, there were nominal decreases shown in patients requiring narcotics and patients needing feeding tubes.
What safety data was reported in the trial?
Patients in the avasopasem group had decreases [across] most of the AEs, [including] oropharyngeal pain, dehydration, radiation, dermatitis, etc. There was a slight increase in mild nausea and vomiting in the avasopasem group, but this typically didn’t reach a grade 3 level.
Patients can have transient drops in blood pressure when they receive the infusion and so sometimes [when] these patients present to clinic, they already have orthostatic hypotension. We would correct that by giving them a prophylactic infusion to improve their hydration status prior to giving the [avasopasem] infusion.
What are the overall implications of this research?
Oncology nurses are at the forefront of caring for patients with locally advanced head and neck cancer—they’re going to be the ones administering the infusions and identifying any adverse reactions to the infusion. This treatment course is especially challenging, and nurses are looking for evidence-based practice solutions that they can use to assist patients throughout treatment. This provides them with a potential solution.
Cullen E, Brown H, Carringer J, Amado A, Pitre L, and Anderson C. ROMAN: phase 3 trial of avasopasem manganese (GC4419) for SOM (SOM) in patients receiving chemoradiotherapy (CRT) for locally advanced head and neck cancer (LAHNC). Paper presented at: 48th Annual Oncology Nursing Society Congress; April 26-30, 2023; San Antonio, TX. Accessed June 7, 2023. https://ons.confex.com/ons/2023/meetingapp.cgi/Paper/12846