Bottom a family of four smiles and laughs at an outdoor table playing a game.
Talia Aron at home with her husband, Chad, and daughters Lily and Abigail. (Photo by Eamon Queeney.)

New Hope

Updated

A man and woman stand next to a playground slide while two young girls sit on the steps, smiling.
Talia Aron at home with her husband, Chad, and daughters Lily and Abigail. (Photo by Eamon Queeney.)

TALIA ARON, MD, WASN’T ALARMED AT FIRST WHEN SHE STARTED TO FEEL SOME NASTY LOWER BACK PAIN. Last September, the medical director at a telehealth company had been traveling to professional conferences for days, sitting on airplanes and in hard-backed chairs.

But instead of getting better when she returned home to Greensboro, North Carolina, the pain got worse. “Looking back at a picture of me [at a conference] in Nashville, I was kind of a grey color,” Aron said.

By the time she saw her OB-GYN, the pain was so bad that her physician sent her straight to the emergency department in Greensboro.

Doctors at first thought that Aron had a kidney stone or infection. Then she was diagnosed with kidney cancer.

When she sought a second opinion at Duke, she received what would turn out to be the correct diagnosis: a urothelial cancer that had already clawed its way into her kidney. Urothelial cancers include all cancers that grow out of cells that line the bladder and the ureters (tubes that drain urine from the kidneys to the bladder).

Historically, people with advanced urothelial cancer live, on average, for sixteen months, with only 10% surviving five years or more on standard-of-care therapy.

But doctors at Duke had a new treatment in mind for Aron that offered her much better odds. The only problem was, the combination therapy, developed by a medical oncologist at Duke Cancer Institute, was approved at that time only for a select population of patients. She would need help from friends and physicians at Duke and beyond to get the best treatment for her.

A woman in a red blouse smiles and looks into the distance.
Talia Aron at home in Greensboro, North Carolina. (Photo by Eamon Queeney)

Getting the Right Diagnosis

After Aron returned home, imaging showed a mass on her kidney, and it was growing rapidly. A urologist in Greensboro scheduled her for surgery to remove the kidney.

But just a few days before the scheduled surgery, James Wantuck, MD, one of her senior colleagues, encouraged her to seek a second opinion through 2nd MD, one of the health benefits offered by their employer, Accolade. That virtual consult — with David Braun, MD, PhD, a genitourinary medical oncologist at Yale School of Medicine — led her to Duke.

“Dr. Braun told me, ‘You are an hour away from Duke. You need to see the best,’” she said.

Braun reached out to Dr Daniel George, MD, a genitourinary medical oncologist at Duke Cancer Institute and co-leader of the center for Prostate and Urologic Cancers. Braun asked that George be on the lookout for Aron. Meanwhile, Aron arranged a meeting with Deborah Kaye, MD, a Duke urologic oncology surgeon, to get a biopsy of her tumor.

Even before seeing the biopsy results, Kaye suspected that Aron’s tumor might not be kidney cancer.

Kaye asked Aron the location of her pain. “When I pointed to my side, Dr. Kaye said that I should not be having pain there if this were kidney cancer. Then Kaye looked very carefully at my previous images and said that she thought I might have urothelial cancer. And she was the first one to have said that,” said Aron.

While Aron was waiting in the clinic for her biopsy results, she started feeling worse. “I was getting rigors — shakes. I couldn’t get warm. I had a very high fever, which I now know is not uncommon with very aggressive cancers, but I didn’t know it then.”

The biopsy confirmed an upper-tract urothelial cancer that appeared like a kidney cancer because it had already spread there.

“Nailing down the specific type of tumor that someone has is critical, because the drugs we use to treat urothelial cancers are completely different from kidney cancer drugs,” said George. “And it’s something we do well at Duke, where we have experts from medical and surgical specialties who work closely with cancer-specific pathologists and radiologists.”

The Tough Road to a New Therapy

The therapy that Aron would ultimately receive is a combination of pembrolizumab, an immunotherapy agent, and enfortumab vedotin, an antibody drug conjugate. Duke medical oncologist Christopher Hoimes, DO, had been studying this combination since 2017.

Hoimes’ reasons for believing that these two agents would work well together were complex, but he boiled down his thinking to this: targeting the cancer’s surface adhesion receptors, which is what enfortumab binds to, could potentially enhance the immune response.

But the odds were against Hoimes in a field where hundreds of cancer therapies and combinations had been tested and failed. Another matter threatening to hinder progress: the drugs he wanted to study were owned by two different companies.

“Companies are typically reluctant to combine their investigational products with an agent owned by another company because the new combination can limit their indications and increase side effects,” said George, who was not involved in the trials. “They must be convinced that a collaboration is worth the risk, extra time, and resources.”

Hoimes was motivated to push for a study of the combination because he was frustrated at watching patients suffer. For years he had seen patients get months of grueling chemotherapy and life-altering surgery that rewarded them with only a small increase in survival. And too many of his patients weren’t even eligible to get the chemotherapy due to other health issues, he said.

After Hoimes and the team of investigators convinced the two companies to work together on a phase 1 study, he led a trial of patients who could not receive standard chemotherapy. Positive data from that trial spawned a phase 2 study, which Hoimes also led.

It was 2019 when George heard Hoimes present data about the new combination at the European Society for Medical Oncologists and decided to recruit him to Duke. “Medical oncologists who specialize in urothelial cancer are rare. We’re lucky to have Chris here, where he is teaching a new generation of young oncologists to manage urothelial cancer patients and conduct clinical research in this space,” said George.

A family of three runs in a grassy yard.
Talia Aron and her husband, Chad, play at home with one of their daughters. (Photo by Eamon Queeney)

Race with the Clock

When Aron landed on Duke’s doorstep, Hoimes’ phase 2 data had already won a hard-earned FDA approval for the promising combinatation treatment. When her insurance company denied the coverage, he called Aron’s insurance arbitrator, who was himself an oncologist, to discuss the unpublished phase 3 data and try to secure Aron a chance to take the new combination before the FDA approval. “At the end of the conversation, he was just as impressed by the data as I was. He actually thanked me for sharing the data and approved coverage for her treatment,” George said.

Aron’s first scan after starting the new treatment showed that tumors in her kidney had shrunk, while tumors in her lung and lymph nodes had disappeared. And her pain diminished to the point where she no longer needed narcotics to manage it. “Not even a Tylenol,” she said. “I’m a little tearful when I talk about it. If it wasn’t for Duke and Dr. George being willing to take me on, I don’t know if I’d be here for my two daughters, who are 9 and 15.”

The outlook for people with advanced urothelial cancer may improve even more in the future, after completion of a phase 3 study of the combination therapy used at an earlier stage: before and after people undergo surgery to try to stop the cancer from spreading. Hoimes is the global lead principal investigator and on the scientific committee for the international study, called Keynote-B15, which fully enrolled patients in the fall of 2023.

“This trial raises the stakes even more. This is the curative-intent setting, where a greater proportion of

patients with urothelial cancer who are candidates for surgery may be cured of their disease,” he said. “I’m

certainly hopeful for similarly stunning results as what we just had for patients who are metastatic, but we need to wait for the data to guide us.”