The pain was subtle. At first, it barely caught Meg Wise’s attention. In November 2019, she felt a twinge under her left shoulder blade and, a few days later, another under her right one. On Christmas, she enjoyed a 40-mile bike ride, but the following day, while hiking, she felt a sharp pain in her hip. Looking back, she said, “It was almost like a public service announcement: Here is the pain.” Wise was 68 and married, a fitness junkie who hadn’t smoked since her mid-20s and now enjoyed biking over 100-mile hilly courses in Dane County. She’d just received a clean mammogram. She was in fine health except for a minor bicycle accident in July. In fact, when she thought of health it was almost always other people’s health.
A trained researcher studying how people live in the face of severe illness, Wise had been working for several years with colleagues on a study focusing on the suffering and resilience of people with advanced cancer.
Given the pain and a small, but noticeable, amount of weight loss, Wise decided to see her doctor. Tests to rule out various conditions followed. Then, on the morning of Jan. 24, two weeks after that initial visit, her doctor, Samantha Sharp, phoned. It was about the bone CT scan Wise had undergone only any hour earlier. The doctor wanted to discuss the results in person. When Wise arrived, Sharp’s face looked ghostly white.
“Meg,” she began, “I have bad news. You didn’t do anything wrong, but you have metastatic cancer.”
The doctor did not know what kind of cancer it was, but additional tests determined it was nonsmall cell lung cancer, which accounts for about 80% of the nation’s 240,000 new lung cancer patients each year.
This could have been the start of another bleak cancer story, a short, grim march to death. Instead, it became a story of modern medicine providing hope where there was none before.
Treatments developed to target specific cancercausing mutations have changed the prognosis for patients with those mutations from months of life remaining to years. Wise’s cancer was caused by what doctors call an ALK positive mutation, which accounts for about 3% to 5% of non-small cell lung cancer cases.
Today, a little more than one in five lung cancer patients live five years after their diagnosis. For those lung cancer patients with the ALK positive mutation who receive targeted therapies, including a drug called alectinib, the five-year survival
rate is a little more than three in five.
“Generally speaking, these medications have been transformative,” said Yasir Elamin, an assistant professor at the University of Texas MD Anderson Cancer Center. “They are well tolerated and have few side effects.”
Side effects can include fatigue, muscle pain, bloody urine, chest pain, increased blood pressure and dizziness.
“Suddenly, we’re not just helping people live for weeks or months longer. We’re helping them live years longer,” said Toby Campbell, a doctor at UW Health specializing in the treatment of lung cancer.
‘I’m not going to be around’
On Jan. 24, 2020, as Wise listened to the doctor describe her condition, she found little to be optimistic about.
Sharp explained that the pelvis was riddled with abnormal tissue called lesions. Meg’s upper lip went numb. She remembers thinking, “What are we going to tell our children?”
At home that evening, she woke from a restless sleep worried about research grants she was applying for. “I can’t go through with these grants,” Meg recalls thinking.
“I’m not going to be around.”
The next day, a Saturday, her daughter-in-law took over the kitchen, filling it with the scents of chicken soup. A large jigsaw puzzle had been spread across a table. But Meg felt too tired to socialize or work on the puzzle. She went to sit by the fireplace swaddled in a blanket.
“As I drifted off,” she said, “I felt like my body, mind and essence dissolving.”
Oh, it would be so easy to float away, she said she began thinking.
“Suddenly, I jolted out of that space and knew it was not my time yet,” she said.
During her study of lung cancer patients, she’d met a doctor who impressed her with his work in palliative care, the way he understood a suffering patient’s experience. The doctor was Campbell, of UW Health. She asked him to lead her care.
Her primary care doctor was fine with the switch.
“I’ll bet you think your body betrayed you,” Campbell said when they met.
That was exactly what she had been thinking.
“The first step,” he told her, “is we need to determine the genetics (of the cancer).”
He ordered an MRI scan of her brain and a blood sample, sometimes called a liquid biopsy. The news from the MRI was not good.
“She was in big trouble. She had cancer throughout her brain,” Campbell said. When cancer attacks the brain, patients often feel headaches, fatigue and dizziness. Wise had not been experiencing dizziness or headaches, making it hard to believe her brain was riddled with cancer.
However, she had been looking very different to her husband, David Tenenbaum.
“I was watching my wife die for a month, and the slope was increasing,” he said. “Meg was good for about three hours a day.”
As for the results of the genetics test, she would have to wait 11 days.
Block the mutation, kill the cancer
On Feb. 18, Campbell called.
“I have really good news for you,” he said.
Wise’s tests showed her cancer had the ALK mutation. The term refers to the rearrangement of two genes called ALK and EML. In affected people, the two genes fuse and form a cancer-causing mutation.
After telling her the good news, Campbell added, “I’m calling an emergency tumor board meeting today.”
Tumor boards are groups of cancer doctors, geneticists and pharmacists who meet to consult on diagnostic and treatment decisions.
“I was so happy,” Wise said of the genetic test result. “I knew I was going to live years, not just months.”
The standard approach for treating patients with cancer that has spread to the brain was to bombard it with radiation. The downside was that the radiation could lead to memory loss or early dementia.
“We didn’t used to worry about that,” Campbell said, “because nobody lived long enough to get that.”
As Campbell recalls, he asked doctors on the board which treatment was best suited to Wise’s cancer. The discussion convinced him that an ALK inhibitor called alectinib was the best option.
The cancer cells needed Wise’s mutated ALK gene for survival.
“The way we talk about it with these mutations is that the cancer is addicted to them,” said Jonathan R. Thompson, a doctor at Froedtert Hospital, who specializes in lung cancer. “So if you block the mutation, the cancer dies.”
Two days before starting on alectinib, Wise received a radiation treatment to shrink the largest lesions on her brain. She meditated to keep her head still during the radiation.
Wise took her first doses of alectinib on the Leap Day, Feb. 29. Four pills at breakfast. Another four pills at dinner. The first week on the medication she also received five, two-minute radiation treatments at the top of her left thigh bone, another area where she had a large lesion.
Her husband asked how quickly the alectinib would start to work. Weeks? Months?
“Oh, I think it will be faster than that,” Campbell said.
Early in her treatment, COVID-19 became a pandemic, and Wise’s next few doctor visits took place by video.
Effective, but not a cure
By her six-week MRI scan, the change was visible. One tumor had shrunk by more than three times — from about 2 centimeters in diameter to 6 millimeters.
She said Campbell was so delighted at the news that he danced a jig.
In June, Wise completed a 50-mile bike ride.
The downside to the new targeted cancer drugs is that they can be very expensive — about $15,000 a month for alectinib — but Wise’s health insurance covered most of the cost.
“Prices are a pretty big issue with these pills,” said Thompson, at Froedtert. “It really depends on the type of insurance the patient has. The big difference is in the co-pay.”
Thompson said some patients face co-pays that are thousands of dollars each month. In such cases, he said, he helps the patients appeal to drug company assistance plans.
The other caveat is that the medications, while effective, are not a cure.
“We see the cancer shrink back incredibly,” said Campbell. However, “unless you kill 100% of the cancer, it will find a way to come back.”
A cat-and-mouse game develops. Once the drug stops the cancer from growing and spreading, the cancer begins seeking a way to get around the blockage. Eventually, the disease is likely to defeat the drug.
However, researchers have learned the routes the cancer takes to bypass the drug, and are continually developing drugs that block the cancer’s alternate routes.
So far, Wise’s cancer hasn’t found a way around the drug, and after discussions with her doctor, she now takes a slightly smaller dose.
At her last visit to Campbell in May, more than two years after her initial diagnosis, Wise received a brief, encouraging assessment from the doctor.
“Nothing growing. Nothing new.”
Mark Johnson wrote in-depth stories about health, science and research for the Journal Sentinel from 2000 to 2022. He is a three-time Pulitzer Prize finalist and, in addition, was part of a team that won the 2011 Pulitzer Prize in Explanatory Reporting for a series of reports on the groundbreaking use of genetic technology to save a 4-year-old boy. Follow him on Twitter: @majohnso.