Patients with pancreatic cancer can obtain molecular tumor profiling through the Pancreatic Cancer Action Network’s Know Your TumorSM precision medicine initiative, a partnership with Perthera, a personalized medicine service company that facilitates the multi-omic profiling and generates the reports to patients and physicians.1,2
At the 2016 Gastrointestinal Cancers Symposium, Lola Rahib, PhD, of the Pancreatic Cancer Action Network, and Michael J. Pishvaian, MD, PhD, of Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, spoke to The ASCO Post about the program. Dr. Pishvaian is also Chief Medical Officer of Perthera.
In an effort to extend the availability of multi-omic profiling to patients with pancreatic cancer in a broad range of clinical settings, the Pancreatic Cancer Action Network and Perthera initiated the Know Your Tumor initiative as an academic, industry, and advocacy group collaboration.
Approximately 500 patients have taken advantage of the Know Your Tumor program, showing its feasibility irrespective of geographic location or access to an academic center. Actionable findings have been identified for 40% of patients.
For Patients and Oncologists
Lola Rahib, PhD
Due to the incredible reach of our Patient Central program, a free resource that assists patients, families, cargivers, and health-care providers by providing vital information about the disease as well as crucial services and resources, we maintain the most comprehensive and up-to-date database of pancreatic cancer clinical trials in the United States,” Dr. Rahib said.
Dr. Rahib emphasized that the Know Your Tumor program markets itself to patients and physicians, though many first hear about the initiative after talking to a Patient Central Associate. She said she would like to see the Know Your Tumor initiative utilized by more oncology providers.
Dr. Pishvaian spoke about its value to oncologists. “The analysis of multi-omic profiling in the context of patient history by a pancreatic cancer specialist provides a service to treating oncologists in the community,” he explained. “A multi-omic approach can reveal a broadened range of molecular alterations that we can harness to make treatment decisions. Our goal is to identify what may be driving the patient’s cancer and provide information that can be used to identify treatment options, including clinical trials.”
Perthera sends the molecular data to a medical review panel of pancreatic cancer experts, who recommend treatment options—many of which are molecularly driven clinical trials. “As a company, we are following these patients for outcomes, trying to assess survival for these patients vs other patients who are not following our options. We are also able to look for prognostic markers,” he said.
How Know Your Tumor Works
Eligible patients identified by the Pancreatic Cancer Action Network’s Patient Central service (877-435-8650; PatientCentral@pancan.org) are referred to Perthera. Perthera facilitates consent, tissue acquisition, and commercial tumor testing as well as generates a number of expert-guided treatment options (made in the context of the patient’s treatment history). A report detailing treatment options is delivered to the patient’s oncologist.
Patients should contact the Pancreatic Cancer Action Network about the Know Your Tumor program early in their disease course, Dr. Pishvaian said. “Sometimes with these patients, we miss the window of opportunity,” he noted.
Collecting Patient Data
Evaluation of these patients, Dr. Pishvaian added, “is systematic, not anecdotal, as we are collecting outcomes data on every patient.”
From June 2014 to December 2015, almost 500 patients were enrolled in Know Your Tumor from 38 states. Physician information was available for 462 of the patients; 66% of these patients were treated at an academic or high-volume center, and 34% were treated in the community.
Researchers obtained and delivered reports on 175 tumor samples. The reports were for second-line treatment in 45% of the cases and for third-line or later treatment for 39%. Of them, 40% revealed actionable findings, primarily through next-generation sequencing. A finding was deemed “actionable” based on a high response rate among patients with that molecular abnormality (in any disease type) or a mechanism/pathway-defined implication of response to treatment.
More than half the patients with actionable alterations were presented with off-label therapy options, and many of the others were recommended for high-priority clinical trials.
Of these 175 cases, 47 patients did not have a treatment change, 34 received therapy consistent with the report (3 off-label targeted therapy and 8 enrolled in clinical trials), 6 received treatment not consistent with the report, and 33 were too sick to receive treatment. Follow-up status was not obtained on 55 patients, Dr. Pishvaian reported.
Common Actionable Finding
Among the actionable findings were alterations in pathways or genes related to the following:
- DNA damage (10%), such as BRCA2, for which platinum-based therapy or a PARP (poly [ADP-ribose] polymerase) inhibitor would be relevant
- Receptor tyrosine kinases (15%), such as ErbB2, for which anti-HER2 therapy is indicated, or an AXL mutation, for which an AXL inhibitor may be beneficial
- Cell cycle (61%), such as CCND1-3 or CDK6, which are targeted by cyclin-dependent kinase inhibitors
- PIK3/mTOR (13%), such as STK11 or AKT2, for which an mTOR inhibitor may be effective
The incorporation of immunohistochemistry refined and expanded the chemotherapy treatment options in all patients, Dr. Pishvaian added.
Dr. Pishvaian gave some examples of the actionable mutations identified and the treatment with which patients were matched. A patient with a RET gene fusion received sunitinib off-label; one with ALK overexpression and BRCA2 mutation received ceritinib (Zykadia) and veliparib on two clinical trials; a patient with TSC2 mutation was treated with everolimus (Afinitor) off-label, and a programmed cell death ligand 1 (PD-L1)–positive patient received nivolumab (Opdivo) and nab-paclitaxel (Abraxane) on a trial. The study has also revealed prognostic markers.
“For patients for whom outcomes data were available, a preliminary assessment of survival for patients who received the recommended options from Perthera, vs non-Perthera–presented options, was suggestive of an improved outcome with Perthera-presented options,” Dr. Pishvaian reported.
“Even if we affect just 10% of patients and dramatically improve their outcomes, or we identify mutations and help patients get into trials, we feel like we have made progress,” he said.
Patients Happy to Aid Research
Jordan Berlin, MD
Jordan Berlin, MD, Professor of Medicine and Clinical Director of the Gastrointestinal Oncology Program, Vanderbilt University, Nashville, commented on the value of the Know Your Tumor program. “This is a novel initiative taken by a patient care organization to increase patients’ awareness of their own tumor and increase their interest in clinical trials that may be designed for their genotype,” he said.
“Right now, we don’t have a lot of treatments for many of the genotypes we find, but we may in the future. And this initiative helps us learn even more,” added Dr. Berlin.
Noting that most patients who are interested will actually not have an actionable mutation—or novel treatment option—Dr. Berlin commented, “Patients understand that sometimes all we get out of this is to learn something. It’s amazingly important to my patients who have, say a p53 or RAS mutation without a treatment option—they are perfectly happy to say, ‘Maybe we learned something for future patients.’” ■
Disclosure: Drs. Rahib and Berlin reported no potential conflicts of interest. Dr. Pishvaian owns stock in Perthera; for his full disclosures, visit http://meetinglibrary.asco.org/content/160193-173.
References
1. Engebretson A, Brody JR, Rahib L, et al: The Know Your Tumor initiative: A national program of multi-omic molecular profiling for patients with pancreatic cancer. 2016 Gastrointestinal Cancers Symposium. Abstract 279. Presented January 22, 2016.
2. Pishvaian MJ, Brody JR, Matrisian L, et al: Multi-Omic profiling for patients with pancreatic cancer: Initial results of the Know Your Tumor initiative. 2016 Gastrointestinal Cancers Symposium. Abstract 282. Presented January 22, 2016.
