Sensitizing drug improves radiotherapy treatment outcomes in advanced pancreatic cancer
Click Here to Manage Email Alerts
Key takeaways:
- Avasopasem combined with ablative stereotactic body radiation therapy extended median PFS compared with placebo.
- No grade 3 or higher treatment-related toxicities occurred in patients who received avasopasem.
The combination of a sensitizing drug and stereotactic body radiation therapy improved treatment outcomes among patients with locally advanced pancreatic cancer, according to study results published in The Lancet Oncology.
Superoxide dismutase mimetics proved effective in sensitizing tumors to stereotactic body radiation therapy, allowing for the safe delivery of high-dose radiation that shrunk tumors not amenable to surgery.
“Surgery currently is the only possible cure for pancreatic cancer, but only 10% to 15% of patients are eligible,” first author Cullen M. Taniguchi, MD, PhD — who died unexpectedly Nov. 14 — said in a press release issued after his death.
“However, there is a large number of patients, about 30% to 40%, with locally advanced disease that can’t be surgically resected,” added Taniguchi, who served as associate professor of gastrointestinal radiation oncology at The University of Texas MD Anderson Cancer Center. “We’ve used radiation therapy for those patients, but we’ve known for some time that traditional dosing is not enough to achieve a meaningful response in most patients.”
Background and methodology
Stereotactic body radiation therapy can potentially serve as a treatment for patients with localized pancreatic ductal adenocarcinoma, and selective dismutase mimetics can sensitize tumors while reducing potential toxicity to normal tissues.
Researchers conducted a double-blinded phase 1b/phase 2 trial to determine the efficacy and toxicity of the selective dismutase mimetic avasopasem manganese (Galera Therapeutics) combined with ablative stereotactic body radiation therapy for localized pancreatic ductal adenocarcinoma.
Eligible patients included adults with borderline resectable or locally advanced pancreatic ductal adenocarcinoma who received at least 3 months of chemotherapy with an ECOG performance score of 0-2 at the time of trial enrollment.
Researchers randomly assigned 42 patients (55% men) in a 1:1 ratio to receive either avasopasem 90 mg daily or placebo infusion bags during stereotactic body radiation therapy (50, 55 or 60 Gy in 5 fractions).
Optimal dose of stereotactic body radiation therapy with avasopasem or placebo as determined by the Late Onset Eff-Tox (LO-ET) beta binomial model served as the study’s primary endpoint.
Results, next steps
Of the total study population, 24 patients received avasopasem and 18 received placebo. However, the placebo arm ended early after failing to meet the study’s prespecified efficacy requirement of greater than 75% local disease control.
Thirteen of 24 patients (54%) in the avasopasem group and 12 of 18 (67%) in the placebo group died during the study treatment period between Jan. 25, 2018, and April 29, 2020.
Although researchers did not design the study arms for comparison, at a median follow-up of 15.6 months they observed a PFS of 12.4 months in the avasopasem arm and 3.4 months in the placebo arm. Combination therapy conferred an 88% overall response rate in the avasopasem arm compared with 67% in the placebo arm.
The avasopasem arm met boundaries for both treatment efficacy and toxicity, while producing a Bayesian model recommendation of 50 Gy or 55 Gy in 5 fractions plus avasopasem for further study.
No treatment-related deaths occurred during the study. Additionally, researchers noted serious adverse events of any cause in three patients (17%) in the placebo arm and six patients (25%) in the avasopasem arm.
Among participants in the placebo arm, grade 3 events included abdominal pain (6%), acute cholangitis (6%) and increased lipase levels (6%).
No treatment-related acute grade 3 to grade 4 adverse events occurred among patients in the avasopasem group.
The results hold promise that adding a selective dismutase mimetic to ablative stereotactic body radiation therapy may help improve treatment outcomes compared with radiation therapy alone for certain pancreatic cancers.
“This trial involved some of the highest doses of radiation ever given to [patients with pancreatic cancer], and it’s notable that even in the control arm these levels of radiation could safely be given with acceptable side effects,” Taniguchi said. “Still, we found there was a significant improvement in overall survival in the arm that received the avasopasem.”
References:
- Taniguchi CM, et al. Lancet Onc. 2023;doi:10.1016/S1470-2045(23)00478-3.
- University of Texas MD Anderson Cancer Center. New combination improves radiation therapy outcomes in patients with locally advanced and borderline resectable pancreatic cancer (press release). Available at: https://www.mdanderson.org/newsroom/new-combination-improves-radiation-therapy-outcomes-in-patients.h00-159623379.html. Published Nov. 29, 2023. Accessed Nov. 29, 2023.
Collapse
Click Here to Manage Email Alerts