Expert Point of View: Laura Dawson, MD
Laura Dawson, MD
Laura Dawson, MD, Professor of Radiation Oncology at the University of Toronto and Princess Margaret Cancer Centre, viewed these initial study results as “a strong signal with high promise.”
“Radiation therapy improves local control and delays local disease progression in patients with pancreatic cancer, but it has not been shown to improve survival in prior randomized trials. Higher doses of radiation therapy are associated with a higher chance of controlling the local tumor for longer. Stereotactic body radiation therapy (SBRT), where highly conformal radiation therapy is delivered in a few large doses per fraction, is one strategy to escalate doses, while shortening the overall radiotherapy time, requiring less time off systemic therapy in patients with unresectable tumors. There is a strong need to investigate strategies like the one studied here that selectively improve the tumor response, without increasing the risk of toxicity,” she explained.
“Surgery is the only curative therapy; thus, therapeutic strategies that include radiation therapy may increase the chance of patients with borderline resectable pancreatic cancer ultimately having surgery with negative (R0) resection margins, with a potential for cure,” Dr. Dawson continued.
“This study is based on elegant preclinical work with an expected increased benefit of superoxide dismutase mimetics with SBRT, aiming to improve the therapeutic ratio in this setting. Unlike many early-phase combined-modality studies, this trial is a placebo-controlled randomized study that attempts to balance for confounding factors. Outcomes, including response rate, local control, and survival, were much improved in the experimental arm compared with the control arm, which is exciting; such a large difference is unusual in radiation therapy studies for pancreatic cancer,” she said.
“Although this signal of increased tumor control with this promising combination is strong, longer follow-up is needed, as the risk of late bleeding increases with time, and this may impact outcomes. Furthermore, there was an imbalance in the patient groups, as more patients in the experimental arm had borderline resectable tumors upfront compared with those in the control arm; not surprisingly, more patients in the experimental arm underwent resection. Patients who undergo resection are likely to have much better survival rates than those who do not,” Dr. Dawson said.
“Of note, the details of chemotherapy were not included in this initial presentation. Further, higher-powered randomized phase III studies are needed before concluding that this approach should change the standard of care. If such studies are conducted, and if they replicate the initial findings and show increased resectability and overall survival of similar magnitude as seen in this study, then this would be a large advance,” she said.
DISCLOSURE: Dr. Dawson has received honoraria from UpToDate and institutional research funding from Merck and is the owner of and receives patent license fees in connection with RaySearch.
Pancreatic cancer is one of the most aggressive, lethal malignancies, and life-extending treatments represent a critical unmet need. A pilot study suggests a potential way forward for patients with nonmetastatic unresectable or borderline resectable pancreatic cancer may be a combination of...