A decade ago, the survival rate for pancreatic cancer hovered around five percent. Today, the five-year survival rate is 10 percent.
“We’ve moved into the double-digits, but there is clearly an urgent need to find better therapies to treat cancer of the pancreas,” said Anup Kasi, MD, MPH, an oncologist at The University of Kansas Cancer Center.
Dr. Kasi has dedicated his career to uncovering new therapies for the treatment of pancreatic cancer, as well as other diseases including colorectal, liver, anal and esophageal/gastric cancers. A physician scientist, Dr. Kasi wears two hats: As a clinician, he treats cancer patients, and as a scientist, Dr. Kasi explores ways to improve therapies by conducting his own clinical studies. At the heart of Dr. Kasi’s work are his investigator-initiated trials (IITs), which he designs and leads himself. Most clinical trials are conducted by the pharmaceutical industry, but IITs allow specialists to take clinical observations and try to improve or develop new therapeutic approaches.
These two roles are enough to keep a person busy, but Dr. Kasi has an unwavering commitment to keep moving the field forward. He is a member of the National Cancer Institute’s (NCI) Pancreatic Cancer Task Force, which is under the NCI’s Gastrointestinal Cancer Steering Committee. In this role, Dr. Kasi and his colleagues evaluate and streamline concepts for pancreatic cancer clinical trials.
“We provide critical feedback to refine the design of clinical trials, ensuring they are feasible, have scientific validity and fit in the portfolio of the NCI’s clinical trial consortium,” Dr. Kasi said.
Dr. Kasi also leads KU Cancer Center’s molecular oncology tumor board. Next-generation sequencing of tumor and inherited genomes has revolutionized cancer treatment. The molecular oncology tumor board convenes experts to discuss the personalized treatment options for specific patients based on their tumor’s genetic profile.
Ongoing and upcoming clinical studies
Every case of pancreatic cancer is different. Dr. Kasi is involved with several clinical studies that look at the biology of the tumor and an individual’s genetic make-up when determining the ideal treatment.
For example, though typically associated with breast cancer, mutations in the BRCA1 and BRCA2 genes also lead to an increased risk for pancreatic cancer. For carriers of mutations in BRCA2, the risk of developing pancreatic cancer is five to 10 percent. BRCA1 genes are estimated to lead to a two to four times increased risk. For those with pancreatic cancer, mutations to BRCA can inform and tailor cancer treatment. Dr. Kasi is leading an ongoing investigator-initiated study called the NIRA-PANC trial. The study is focused on unresectable and metastatic pancreatic cancers that harbor DNA repair defects, including BRCA1 and BRCA2. This trial is open and currently accruing.
Dr. Kasi serves as study co-chair and co-principal investigator (PI) for a multi-site clinical trial studying people with pancreatic cancer who have the BRCA1 or BRCA2 mutation. Called the APOLLO study, patients who have already undergone chemotherapy and surgery are randomized to receive a PARP inhibitor. Dr. Kasi received the NCI-SWOG Young investigator Award for developing this protocol. The trial will be available at The University of Kansas Cancer Center.
“Patients with breast or ovarian BRCA-related cancer benefit from targeted therapies,” Dr. Kasi said. “This study will explore the same concept for pancreatic cancer.”
An investigator-initiated study also opening soon and led by Dr. Kasi will look at modifying the tumor microenvironment. When a cancerous tumor forms, a fibrous, stromal-like barrier can encapsulate it, making it difficult for therapies to penetrate. The tumor microenvironment is also immunosuppressive. Converting pancreatic cancer from “cold” to “hot” will make the tumors more amenable to immunotherapy.
“In this study, we will add an agent to chemotherapy that will allow medication to pierce the microenvironment,” Dr. Kasi said. “The very first patient in the US will be dosed with this agent at The University of Kansas Cancer Center.”
Dr. Kasi is also designing a trial that will combine immunotherapy with a vaccine against KRAS gene mutations. Up to 95 percent of people with pancreatic cancer have this mutation. Up until 2021, when the U.S. Food & Drug Administration approved the first-in-class KRAS-G12C inhibitor for non-small cell lung cancer, the KRAS mutation had previously been undruggable.
“There are many types of KRAS mutations, including KRAS-G12D, which is much more common than KRAS-G12C,” Dr. Kasi said. “Therefore, the vaccination will target a group of KRAS mutations. The aim of the trial is to prevent the cancer from returning.”
In addition, Dr. Kasi is leading ongoing clinical trials studying a combination of targeted therapy and chemotherapy for people with advanced pancreatic and colorectal cancers who have KRAS mutations.
As pancreatic cancer survival rates inch upward, Dr. Kasi, who was named a Pancreatic Cancer Action Network (PanCAN) Patient Champion in 2021, is committed to continuing his urgent journey to find more effective, personalized treatments.
“The drugs available today are better tolerated and have improved survival to some extent,” Dr. Kasi said. “But there’s always room to improve pancreatic cancer survival rates and outcomes.”
By: KU Cancer Center