Key advances in veterinary oncology

At a recent dvm360® webinar, Philip Bergman, DVM, PhD, MS, DACVIM (oncology), director of clinical studies for VCA Animal Hospitals, an adjunct faculty member at Memorial Sloan Kettering Cancer Center, and principal veterinarian investigator for the canine melanoma vaccine, Oncept, discussed recent advances in veterinary oncology for viewers to put on their radar.

“Let me start by saying that I’m a proud member of the Pet CancerCare Alliance, which brings together about 30 individuals across our international VCA Animal Hospitals network,” Dr. Bergman said. “This group includes medical oncologists, radiation oncologists, surgical oncologists, pathologists, technicians, radiologists, and an anesthesiologist. This alliance gets us out of our silos and positions us to tackle some of the biggest problems that we have in veterinary oncology together.”

“That collaboration helps shape my thinking about recent advances in oncology. And still, I’d like to acknowledge that every oncologist’s list of ‘most important advances’ could be different. My goal, though, is to share the advances that I believe will make the biggest difference for oncology patients in your hospital tomorrow.”

Here’s the list of oncology updates that Dr. Bergman shared:

1. Rabacfosadine Injection

Rabacfosadine injection (Tanovea CA-1; VetDC, Inc) is designed to target and kill canine lymphoma cells. It was conditionally approved in 2017 for the treatment of canine lymphoma and received full FDA approval in July 2021.

“This was the first treatment we had for canine lymphoma that was not a hand-me-down from human medicine. Tanovea certainly has the typical type of spectrum that you expect for a cytotoxic chemotherapy, with mild to moderate gastrointestinal and bone marrow [adverse] effects. Although they are rare, we do see other adverse effects. Up to three percent of dogs can have significant hyporexia to full blown anorexia for as long as two weeks. We see some skin toxicity, so we think that the drug tries to localize to that area. That suggests it could have some good activity with skin-based lymphoma or mycosis fungoides.” Bergman told viewers. “Bottom line, we’re really happy to have this drug in our toolkit.

2. Tigilanol tiglate injection

Tigilanol tiglate injection (Stelfonta; Virbac) is an intratumoral therapy approved by the FDA in November 2020 for the treatment of nonmetastatic cutaneous mast cell tumors in dogs. This agent is a protein kinase C activator that stimulates rapid tumor destruction, said Dr. Bergman.

“With this very effective agent, we see complete disappearance in 75 percent of cases to upwards of 90 percent. Given what we’ve seen to this point, there’s also a chance that this treatment could provide an abscopal effect. So when we inject and destroy a tumor at one site, a similar tumor with a similar name at a different site goes away due to immune based mechanism. If we’re able to prove that this treatment has an abscopal effect, that would be groundbreaking.

“It’s key to know that with this agent, full tumor destruction leaves a hole in the patient’s tissue,” he explained. “With these cases, we typically don’t use E-collars, because the wounds don’t get infected when the dogs lick them. We’ve seen that this open wound has healthy granulation and heals incredibly quickly in the vast majority of patients.

“One downside that’s worth mentioning: Due to the volume limitation of injection, you can only treat relatively small mast cell tumors. They need to be less than eight centimeters cubed, or about the size of a dime.”

3. Chest CT Imaging

Computed tomography (CT) is available at most veterinary specialty practices, and these scans offer a significant advantage in identifying pulmonary metastases.

“To see signs of metastasis on radiographs, the growth needs to be 5 to 8 millimeters. But with a CT, you can reliably see growths as small as 1 to 2 millimeters,” said Dr. Bergman. “In fact, a study conducted by researchers at the University of California, Davis found chest X-rays identified histologically confirmed pulmonary metastasis nine percent of the time, compared with 100 percent identification on CT scans."

“This is critical to reliably stage patients. So I think of this as a key step for providing a clear ‘go’ or ‘no-go’ when deciding whether to move forward with any significant procedure, whether it’s a surgery, radiation treatment, or something else,” said Dr. Bergman.

4. Maropitant citrate

Maropitant citrate (Cerenia; Zoetis Petcare) is used to treat vomiting and motion sickness in dogs and cats. “When we discuss these new tools in person, I typically ask who’s using Cerenia, and a show of hands says 99 percent of veterinarians. That’s great. We have something that’s specifically for dogs and highly efficacious. I’m glad we’re using it!” said Dr. Bergman.

“Research shows that in human medicine, doctors and nurses grossly underpredict the amount of delayed nausea and vomiting in chemotherapy patients—and I suspect that happens in veterinary medicine, too. Of course, quality of life questions weigh heavily on both pet owners and veterinarians when they’re making treatment decisions. So we want to minimize nausea and vomiting as much as we can. In that spirit, I’m currently prescribing prophylactic use of Cerenia for my Doxorubicin patients for the five days following treatment.”

5. Toceranib phosphate

Toceranib phosphate (Palladia; Zoetis Petcare) is the only antiangiogenic, antiproliferative therapy specifically developed for canine mast cell tumor treatment.

“The FDA pivotal study for Palladia was double-blinded and randomized with placebo control. The results showed there was an increased response rate and length of response with Palladia compared to placebo. Overall response was about 60 percent—similar to the result delivered by multi agent chemotherapy,” said Dr. Bergman. “Furthermore, we also know that Palladia can have activity against a variety of other tumors when used off-label. Therefore, if you have a patient that has not responded to classic standard of care, pick up the phone and talk to your favorite local oncologist to see if the tumor you’re treating could be on the list of Palladia-responsive tumors.”

6. Canine melanoma vaccine, DNA

The canine melanoma vaccine, DNA (Oncept; Merial) is used to extend survival time in dogs treated for canine oral melanoma. The vaccine is produced with xenogeneic plasmid DNA that contains DNA for human tyrosinase (huTyr), resulting in the production of a human antigen that is homologous to canine tyrosinase (cTyr) but recognized as foreign by the dog’s immune system.

“Chemotherapy has poor efficacy against melanoma. In fact, some recent papers show that chemotherapy affords no survival benefit for dogs with melanoma. In oral melanoma cases, dogs typically present with stage two and stage three melanoma. Normally those patients with standard of care treatment options such as surgery, radiation and chemotherapy have three to six months to live on average. We’re seeing much, much longer survival times with the addition of Oncept.”

7. Flow cytometry

Flow cytometry immunophenotyping helps diagnose and classify blood cell cancers to identify the most effective treatment options.

“For many years, we did not do flow cytometry because we didn’t know to differentiate B-cell lymphoma patients from T-cell lymphoma patients. Now we know that patients with T-cell lymphoma have a worse prognosis and we identify them and treat them differently,” said Dr. Bergman. “It’s such a critical advancement that we can better align the treatment and agent to the type of tumor.”

8. Minimally invasive urine test

Research findings have revealed that a droplet digital polymerase chain reaction test can identify the BRAF mutation (changes in the DNA of some cancer cells) in free catch urine samples from approximately 85 percent of canine urothelial carcinoma and prostatic carcinoma patients.

“I can’t say enough positive things about this urine test,” said Dr. Bergman. “One thing that’s particularly interesting is that there are a number of breeds that commonly develop these cancers. While it’s possible to see this in any breed, I tend to think of Westies, Scotties, beagles, Australian Shepherds, and Border Collies—typically older than six years. Studies are underway to investigate use of this tool less as a diagnostic and more as a true screening test to try to pick this up early, before the cancer invades muscle or serosal tissues.”

9. Treatment of extravasation

“Even a couple of drops of Doxorubicin or Adriamycin cause an exquisitely painful wound that takes many months to heal—if it ever does. Many patients undergo amputation. So it’s critical to prevent this from happening. And then sometimes we still face these unfortunate situations,” said Dr. Bergman. “We’ve learned that if you inject Dexrazoxane by IV within a couple of hours of the extravasation, you can abrogate the extravasation reaction.”

10. Identification of MDR1 mutation

Dogs with MDR1 mutation show sensitivity to agents that are P-glycoprotein substrates. While many chemotherapy agents are P-glycoprotein substrates, there are many more drugs outside of oncology that are also P-glycoprotein substrates.

“What you’ll appreciate when you look at the frequency with which specific breeds carry this mutation is that this can really occur in any patient. That’s why we’re frequently testing our oncology patients when they need chemotherapy agents that are P-glycoprotein substrates."

“While I’m obviously focused on avoiding adverse effects of oncology treatments, P-glycoprotein substrates are used in veterinary medicine in a wide range of contexts. Given that reality and the relatively large population of some dogs who carry the MDR1 mutation, I’d argue we should consider testing puppies for the mutation, so we have this information in patients’ files before we really need it,” said Dr. Bergman.

This webinar was sponsored by VCA and the Pet CancerCare Alliance. The Pet CancerCare Alliance (PCCA) is VCA’s interdisciplinary group of oncology professionals. The PCCA is led by an advisory board whose goal is to raise the level of pet cancer care industry wide, through education, research, consultation and development of pioneering treatments aimed at improving outcomes for pets living with cancer. To watch the full webinar on demand, visit [url map to this link: https://globalmeet.webcasts.com/viewer/ event.jsp?ei=1470382&tp_key=aff36d1b80].