by A recent study conducted by researchers at the University of Texas MD Anderson Cancer Center and Moffitt Cancer Center has found that combining sensitizing drugs with a specific type of radiation therapy can improve outcomes for patients with locally advanced pancreatic cancer. The combination therapy resulted in higher progression-free survival (PFS) and overall response rates (ORR).
The study, published in The Lancet Oncology, focused on a class of drugs called superoxide dismutase mimetics, which effectively sensitized tumors to stereotactic body radiation therapy (SBRT). This allowed for the safe delivery of higher radiation doses that can shrink tumors when surgery is not a viable option.
According to Dr. Cullen Taniguchi, associate professor of Gastrointestinal Radiation Oncology at MD Anderson, currently, surgery is the only potential cure for pancreatic cancer, but only a small percentage of patients are eligible. However, there is a significant number of patients, about 30-40%, who have locally advanced disease that cannot be surgically resected. Traditional radiation therapy has not been effective in achieving meaningful responses in these patients.
The introduction of SBRT has shown promise in this setting. SBRT delivers a more focused beam of radiation over a shorter time frame, usually five days compared to several weeks with traditional radiation. This technology allows clinicians to shrink tumors more effectively and achieve significant responses, therefore increasing the possibility of surgery for more patients.
Although SBRT has improved survival rates and reduced disruption to patients’ lives, it is not a cure for most cases. To achieve better outcomes, higher radiation doses need to be delivered to the tumor. This study aimed to either reduce the effects of SBRT on normal tissue or make the radiation more toxic to the tumor using superoxide dismutase mimetics.
The researchers combined the advancements in SBRT with a superoxide dismutase mimetic called avasopasem manganese. The trial compared the efficacy and toxicity of SBRT plus placebo to SBRT plus avasopasem manganese. The results showed a significant improvement in progression-free survival, with a median PFS of 12.4 months in the combination arm compared to 3.4 months in the placebo arm. The overall response rate was also higher in the treatment arm (88%) compared to the placebo arm (67%).
Superoxide dismutase mimetics are synthetic forms of enzymes that break down the byproducts of radiation therapy. In healthy cells, these enzymes break down the byproducts, preventing damage to cells and allowing them to replicate. However, pancreatic cancer cells do not have the same ability to break down these byproducts, leading to a build-up of harmful substances and cell death. The superoxide dismutase mimetics increase the ability of healthy cells to deal with the byproducts, while simultaneously increasing their build-up in cancer cells.
This trial involved administering some of the highest doses of radiation ever given to pancreatic cancer patients. Remarkably, even in the control arm, these high levels of radiation could be safely delivered with tolerable side effects. However, the arm that received avasopasem demonstrated a significant improvement in overall survival.
The study involved 42 participants with a median age of 71. The majority of patients were male (67%) and white (88%), with an average of 18 weeks of prior chemotherapy treatment. No dose-limiting toxicities or treatment-related adverse events of grade three or higher were observed in either arm, and the incidence of treatment-related adverse events of any grade was similar in both arms.
The interim data from this study was presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting in 2020. The promising results have led to an expanded Phase II trial (GRECO-2), which has recently concluded.
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1. Source: Coherent Market Insights, Public sources, Desk research
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