It’s currently known that the exceptional responses in pancreatic cancer do not appear to be related to the treatment received or the underlying genetic mutations in these patients. Evidence does suggest, however, that these exceptional responses may somehow be immune-mediated.
In a study published in Nature, Dr Balachandran and colleagues found that the patients with pancreatic cancer who had more immune cells, specifically T cells, in their tumor lived longer.2 “We think that the T cells are recognizing specific mutations in their tumors that makes these tumors sort of more immunogenic,” said Dr Balachandran. “Like red flags for the immune system.”
The multitumor Australian program will collect blood samples for germline analysis and analyze archival tissue samples for genomic analysis and further tests, as appropriate. Additional testing may be determined by tumor type, but no specific plans have been made yet to answer tumor-specific questions, such as whether T cells indeed recognize specific mutations in pancreatic tumors.
S. Percy Ivy, MD, associate chief of the investigational drug branch at the National Cancer Institute (NCI), told Cancer Therapy Advisor that while the Australian program may not contribute a “massively large” number of patients due to Australia’s population size relative to that in the United States, they will bring a “rigorous” scientific approach.
“They have set up a high-quality program, just like any of the rest,” Dr Ivy said. She was the principal investigator of the Exceptional Responder Initiative pilot study (ClinicalTrials.gov Identifier: NCT02243592). “They’ll be able to find some very unique insights from these patients.”
One unique aspect of the Australian program that has already emerged is the number of patients with mesothelioma the investigators were able to accrue. “Australia has a very high rate of mesothelioma,” said Dr Barnet. “We have the potential to develop a study around that subset that perhaps would be difficult to run elsewhere.”
The study is also recruiting patients who have had exceptionally poor responses, such as those who experience the controversial phenomenon known as disease hyperprogression — but these patients are especially hard to recruit because their disease progresses quickly and therefore, they are usually unable to provide consent. None of these patients have been recruited so far.
“We’re looking to get a specific ethics approval to [get] consent next of kin for that part of the study, because it may also be an important comparative group for the exceptionally good responders,” said Dr Barnet.
- Barnet M, Pathmanandavel S, McCarthy L, Goodnow C, and Joshua A. The Australian Exceptional Responders Program: A national collaboration [published online October 1, 2019]. Ann Oncol. doi: 10.1093/annonc/mdz268.104
- Balachandran VP, Łuksza M, Zhao JN, et al. Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer. Nature. 2017;551(7681):512-516.