Nearly a third of people diagnosed with pancreatic adenocarcinoma have locally advanced tumors that cannot be removed by surgery. A longstanding and critical question for these patients is whether adding radiation to chemotherapy provides any benefit.
Alas, the answer appears to be no, according to the recently completed LAP07 study, which was stopped early when an interim analysis failed to demonstrate a benefit in overall survival. While disappointing, the finding fits with the emerging view that pancreatic cancer is a disease with a multitude of subtypes responding in diverse ways to therapy.
Given our rapidly expanding understanding of pancreatic cancer subtypes with both prognostic and therapeutic relevance perhaps the failures of too-numerous-to-count pancreatic clinical trials (including LAP07) should come as no surprise. Most pancreatic cancer trials never had a chance to find a signal of activity in this ocean of disease heterogeneity.
Thus, LAP07 succeeds in that it confirms and underscores the complex biology that we are discovering scientifically and that we observe clinically and challenges us to raise our game.
Going forward, they assert, all clinical trials should mandate the collection of tumor and blood before and after treatment for biomarker and bioresponse correlative studies that can inform the next generation of molecularly defined subgroup-driven trials. “As our knowledge of pancreatic cancer biology grows,” they say, “we owe it to patients to start applying that knowledge in novel clinical trial designs.”
Vaccaro is a clinical associate professor, and Lopez an associate professor, in the Division of Hematology and Medical Oncology in the OHSU School of Medicine. You can read the full commentary online at the JAMA Network.
Chemoradiation for Locally Advanced Unresectable Pancreatic Cancer—What Now? by Gina Vaccaro and Charles D. Lopez, JAMA Oncology, August 4, 2016
Effect of Chemoradiotherapy vs Chemotherapy on Survival in Patients With Locally Advanced Pancreatic Cancer Controlled After 4 Months of Gemcitabine With or Without Erlotinib: The LAP07 Randomized Clinical Trial by Pascal Hammel and others, JAMA, May 3, 2016