Exploring new treatment options for a devastating cancer
Delivering the news to a grieving pet owner that their dog’s cancer is likely not curable—even with the most aggressive treatment possible—is one of the hardest tasks in veterinary medicine.
Hemangiosarcoma has been deemed a “silent killer,” in the words of Nicola Mason B.Vet.Med, PhD, DACVIM (Internal Medicine), FCPP, MRCVS, professor of medicine at the University of Pennsylvania School of Veterinary Medicine, because it’s often not diagnosed until a seemingly healthy dog suffers from acute collapse due to a ruptured, bleeding tumor, usually on the spleen.
Even in cases where no metastasis is noted, hemangiosarcoma usually has already started to spread. With splenectomy and aggressive chemotherapy, the average life expectancy post-diagnosis is six months.
In an effort to change this grim prognosis, Mason is the principal investigator for a new clinical trial at the University of Pennsylvania School of Veterinary Medicine that will examine the safety and efficacy of copanlisib—a phosphoinositide 3-kinase (PI3K) inhibitor—as a potential new treatment in the arsenal to slow the growth and spread of metastatic splenic hemangiosarcoma.
Copanlisib in human medicine
Copanlisib is a chemotherapy drug that is currently used clinically to inhibit the growth and spread of many human cancers such as follicular lymphoma. It is often used in patients whose cancer has become refractory to other chemotherapy drugs. Because of the ubiquity of PI3K mutations in human cancers, PI3K inhibitors have also been used and/or studied to treat leukemias, glioblastoma, prostate cancers, endometrial cancer, colorectal cancers, breast cancers, pancreatic adenocarcinoma, hepatocellular carcinoma, ovarian cancer, and more.
Researchers at Penn Vet and other institutions have determined that approximately 50% of all canine splenic hemangiosarcoma cases contain a mutation in the PI3K gene. In vitro studies using canine cell lines, including hemangiosarcoma cells, have demonstrated a good response to PI3K inhibitors, but up until now, no in vivo studies have been performed in dogs affected with hemangiosarcoma.
As Mason explains, “Now that we have identified this genetic mutation as a potential driver of splenic hemangiosarcoma, we can specifically target that driver with a drug in an approach known as precision medicine.” Other PI3K inhibitor drugs are currently being studied in the treatment of canine lymphoma.
Potential risks of copanlisib
As with other chemotherapeutic drugs, copanlisib carries risks of toxicity. Mason reports that the PI3K pathway is part of the functionality of many noncancer cells as well. The primary systems of concern for toxicity are the gastrointestinal tract and the liver.
Other risks associated with copanlisib can include acquired resistance of the cancer cells to the drug. If this proves to be the case in the treatment of hemangiosarcoma in dogs, future studies may look at the use of copanlisib in combination with other drugs to help combat resistance.
Penn Vet enrolling study participants
Penn Vet’s clinical trial is currently enrolling patients who have been diagnosed with splenic hemangiosarcoma and had a splenectomy, who have no evidence of metastasis, and who have not been treated with any chemotherapy drugs, holistic treatments, or supplements.
Study participants will be given weekly intravenous injections of copanlilsib for three weeks, have one week off, and then repeat the cycle three more times, increasing the dose each cycle. Patients will be monitored for signs of toxicity and for evidence of metastasis of their hemangiosarcoma. Five follow up visits will be conducted over the first year. All costs associated with treatment will be covered by the study.
Veterinarians who have potentially eligible patients in the Philadelphia area are encouraged to reach out to the Veterinary Clinical Investigations Center (VCIC) at the University of Pennsylvania at (215) 573-0302 or [email protected].
Hopefully this study and others like it will result in more favorable treatment options and a better prognosis to present to dog owners when delivering that dreaded diagnosis.
Further reading
Penn Vet Veterinary Clinical Investigations Center website, including information on this clinical trial:
https://www.vet.upenn.edu/research/clinical-trials-vcic/all-clinical-trials/clinical-trial/use-of-the-pi3k-inhibitor-copanlisib-to-treat-splenic-hemangiosarcoma
AVMA database of veterinary clinical studies:
https://www.avma.org/resources-tools/find-veterinary-clinical-studies
The PI3K pathway in human disease:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726441/
Copanlisib Injection:
https://medlineplus.gov/druginfo/meds/a617044.html
Targeting PI3K in cancer: mechanisms and advances in clinical trials:
https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-019-0954-x
Emily Singler, VMD, is a 2001 graduate of Penn State University and a 2005 graduate of University of Pennsylvania School of Veterinary Medicine. She has worked in shelter medicine, private practice, and as a relief veterinarian. She currently works as a veterinary writer and consultant and has her own blog, www.vetmedbaby.com. Emily also writes a monthly column for NEWStat exploring One Health and the human-animal bond.
Photo credit: © OlenaKlymenok E+ via Getty Images Plus