Article
Author(s):
The authors said their study is the first to show that targeted treaments for patients with certain molecular alterations could be a possibility in pancreatic cancer.
New research out this week from The Lancet Oncology says targeted treatments for pancreatic cancer—one with a poor prognosis—may help certain patients live an extra year.
The authors said their study is the first to show that targeted treaments for patients with certain molecular alterations could be a possibility in pancreatic cancer. Other studies have shown that up to 25% of patients have these molecular alterations. In this work, the authors analyzed information from patients who had been prescribed targeted therapy.
Pancreatic cancer is often diagnosed late, with few treatment options and low survival rates; fewer than 1 in 10 patients live for 5 years or more after diagnosis. Globally, there were 458,918 new cases reported in 2018; in the United States, it affects nearly 57,000 Americans annually.
About 4% to 7% of patients with pancreatic cancer have a germline BRCA mutation; overall, the number of patients with a particular molecular alteration are too low to carry out a clinical trial. In this study, the authors carried out a retrospective analysis of data from the Pancreatic Cancer Action Network’s Know Your Tumor program, a patient registry for those who have had molecular testing.
On an off-label basis, the patients were treated with a targeted therapy that matched their molecular alteration, even though the treatment was not originally approved for pancreatic cancer. In the observational study, those who received the targeted therapy alongside other treatment survived for an average of 1 year longer after being diagnosed with advanced disease, compared with patients who received standard chemotherapy (survival of 31 vs 18 months).
Of 1856 patients with pancreatic cancer in the program between June 16, 2014, and March 31, 2019, 1082 (58%) patients received reports based on their molecular testing results.
Of the 1082, 26% (282) were found to have tumors with molecular changes that were potentially susceptible to targeted therapies.
Treatment outcomes were only available for 189 of these patients; some had died and others lacked documented treatment information.
Of the 189, 46 patients had received a targeted therapy matched to the specific molecular change. They were the ones who survived an extra year.
After a median follow-up of 383 days, treatment targeting actionable mutations led to a median overall survival (OS) of 2.58 years as compared with 1.51 years for patients who had actionable mutations but did not receive targeted therapy (143 patients), P =.0004.
The 488 patients without actionable mutations had a median OS of about 16 months, also significantly worse than the patients with actionable mutations treated with matched therapies (hazard ratio [HR] 0.34; 95% CI, 0.22-0.53, P <.0001).
Median OS did not differ significantly between patients treated with unmatched therapies and those without actionable mutations.
“Our study provides strong rationale that tumour-based molecular profiling for patients with pancreatic cancer should be routinely
performed and encourages prospective clinical trials based on this or similar platforms,” the authors wrote.
In 2019, the FDA approved the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib (Lynparza) for BRCA-mutated pancreatic cancers. PARP inhibitors kill cancer cells by blocking enzymes that let the cells repair DNA.
In a statement, the authors said one limitation is that many of the patients who received a targeted therapy were also treated with other therapies at the same time, making it difficult to definitively determine the precise benefits of this approach over standard care. However, because both groups received chemotherapy, the only variable was whether or not the patients also received the molecularly targeted therapy.
Reference
Pishvaian MJ, Blais EM, Brody JR, et al. Overall survival in patients with pancreatic cancer receiving matched therapies following molecular profiling: A retrospective analysis of the Know Your Tumor registry trial [published online March 2, 2020]. Lancet Oncol. doi: 10.1016/S1470-2045(20)30074-7.
Oncology Onward: A Conversation With Penn Medicine's Dr Justin Bekelman
Incorporating Discussions of Cannabis Use Into Oncology Care Visits