The prognosis for John Middleton is not good.
The 43-year-old engineer from Asheville, North Carolina, suffers from a type of bile duct cancer hidden in the liver called cholangiocarcinoma. It is a rare type of cancer, diagnosed in about 8,000 people a year in the United States, according to the American Cancer Society.
This is a lethal variant. The National Cancer Institute states that only 22% of patients live five years after diagnosis.
Middleton has about 18 months to live.
“I know we’re not guaranteed tomorrow,” he said, “but I feel like I’m looking at a stopwatch with an expiration date. It’s very scary.”
Her oncologist, Dr. Martin Palmeri of Messino Cancer Center in Asheville, said Middleton’s best option is a liver transplant. Middleton has a willing donor: her identical twin brother, James.
“In theory, that could cure it,” Palmeri said.
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However, to be healthy enough to undergo the transplant, Middleton needs to keep his cancer at bay for six to nine months. A new drug, approved last year by the Food and Drug Administration (FDA), is your best chance to achieve this.
The drug, Ziihera, targets the specific genetic fingerprint of her cancer, according to her doctors.
In March, Palmeri contacted Middleton’s insurance company, Cigna Healthcare, to obtain prior authorization for the medication.
Cigna denied the request, stating in the denial letter that Middleton should try other medications first.
Palmeri stated that these medications are also “very inferior.”
“The problem is, if it fails and the cancer spreads outside the liver to another part of the body, then your chances of healing would disappear“he explained.
Palmeri appealed twice on Middleton’s behalf, but only received two more denials.
Ziihera’s “application was carefully reviewed by several medical directors, including two board-certified hematology and medical oncology specialists independent of Cigna,” a company spokesperson said in a statement to NBC News. “There are several medications covered by Mr. Middleton’s plan that are similar to Ziihera and recommended for his current condition.”
All of these drugs target and bind to a protein on cancer cells called HER2, which helps slow or even stop the multiplication of those cells.
Cigna eventually approved a similar drug, called Enhertu.
But research shows that it is not as effective against cancers as Middleton’s for much longer than about six months. That’s probably not enough time, Palmeri said, for Middleton to undergo a liver transplant.
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“In my opinion, that is playing ‘cancer Russian roulette,'” Palmeri said. “It’s just not morally right.”
Middleton said he will begin treatment with Enhertu this week.
“It’s really heartbreaking to not get what the science says you should get,” she said.
The mortality rate of cholangiocarcinoma is high because the cancer is usually diagnosed in advanced stages, when it is more difficult to control.
Doctors discovered Middleton’s cancer by chance at an early stage. In 2023, he underwent an MRI to determine if he had Crohn’s disease, an inflammatory bowel disorder. However, the images showed worrying spots on the liver.
Middleton began treatment immediately: surgery, chemotherapy and radiotherapy. He was cancer-free until last February, when he suffered a relapse. He underwent a second surgery and another round of chemotherapy.
According to Palmeri, Ziihera should have been the next step.
In a clinical trial by the drug manufacturer, 62 patients with cholangiocarcinoma received Ziihera. To be included in the trial, patients could not have previously taken a HER2 drug for their cancer.
However, Cigna denied the request, saying Middleton could only receive Ziihera if she had already taken an anti-HER2 medication.
“The problem is that there is no evidence to justify using Ziihera AFTER prior HER2 treatment,” Palmeri wrote in a text message.
In the trial, more than half (52%) of the participants responded satisfactorily to the drug. Among those who did, the effects lasted an average of 15 months.
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“More than 50% is incredible for a second-line therapy,” said Dr. Nipun Merchant, chief of the division of surgical oncology at Sylvester Comprehensive Cancer Center at the University of Miami Health System. “We don’t see that very often.”
Dr. Douglas Rubinson, a gastrointestinal cancer physician at the Dana-Farber Cancer Institute in Boston, said Ziihera “may be the first major breakthrough targeting HER2” in gastrointestinal tract cancers.
Still, he was careful not to promise that a liver transplant would cure Middleton.
“There are now some publications describing encouraging efforts in the area of liver transplantation and that are prompting more studies,” Rubinson said. “But we’re not yet at the point where we can say this is a standard strategy.”
Neither Rubinson nor Merchant is involved in Middleton’s care.
The Middletons are a very loving family.; Hugs are frequent and spontaneous.
Middleton and his wife, Caitlin, live 10 minutes from his brother James and his family. His mother, Linda, lives 10 minutes in the other direction, still in the house where she raised her children, in the shadow of North Carolina’s Blue Ridge Mountains.
Whether on purpose or not, Middleton and his identical twin, about to turn 44, still dress the same, in baseball caps and plaid shirts. The two men talk almost daily.
“John is my best friend,” James said. “Getting that medicine could save your life. You could get a liver, my liver.”
On a cool October day, the brothers walked around the Middleton property, discussing which trees needed pruning. He said his grass was growing too long. James promised he would return over the weekend to cut it, something Middleton can no longer do.
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They, along with their wives, dream of one day living on the same land, working together.
“If I can’t take Ziihera and things don’t go very well, my chances of living will be between two and possibly six years,” he said. “It’s hard knowing my dogs will outlive me. I worry about my wife and my mother.”
“I have a lot of people I have to support and take care of,” he said.
