At the forefront of lung cancer battle

Results of a clinical trial show that a new drug may become the first-line treatment for lung cancer patients with the ALK genetic mutation.
January 2nd, 2019

Sheri John’s life has mostly been a model of stability. A Colorado native with farming roots in the soil near Sterling, she moved to the Denver area in grade school, graduated from Sheridan High School in 1976 and became a dental assistant. Over the past 38 years, she’s applied her skills at precisely two places – the last one for 21 years and counting.

Now 61, John has also kept her life on an even keel. She doesn’t smoke or drink and says she stuck to the straight and narrow, even in her younger years.

“I was not a wild child in school,” she said.

Sheri John with Lassie, her agility dog
Sheri John with Lassie, her agility dog.

In addition to job and family, John puts her energy into agility training for dogs, a pursuit that requires plenty of stamina. Taking her dog – Lassie, appropriately enough – through his paces on the twists and turns of an obstacle course was no sweat until the summer of 2016. She’d had a cold and gotten treatment for it. But the symptoms hung on, and John found herself short of breath when she ran with Lassie.

“When I can’t run my dog on a course I’ve been doing for 10 years, I knew something was wrong,” John said. She stuck it out, but in October 2016, knifing back pain derailed a planned trip to Kansas and sent her to the hospital for what turned out to be a kidney stone. However, tests revealed a far greater problem.

Stunning news, with a twist of hope

Sheri John was to face life’s great destabilizer: cancer. Specifically, it was lung cancer, the leading cause of cancer deaths in women. Adding to the shock, John had the most advanced form, stage IV, meaning that the cancer had spread to other parts of her body. The first oncologist she met with bluntly told her she had six months to a year to live.

“I was numb,” John recalled. Her mind began whirling through all she needed to prepare for in the time she had left: saying good-bye to her husband and family, finding a home for her dog, shedding possessions.

“I felt like I was at the end,” John said.

Lassie jumps over an obstacle during agility training.
Sheri’’s lung cancer treatment has allowed her to once again keep up with Lassie on his agility training.

Two years later, John has changed oncologists and is still here and battling back with the aid of a lung cancer-fighting drug, brigatinib, she receives through the UCHealth University of Colorado Hospital on the Anschutz Medical Campus that has shown promising results in clinical trials conducted by the University of Colorado Cancer Center. Brigatinib is the latest generation of drugs that inhibit an acquired genetic mutation, ALK, that occurs in about 4 percent of people with non-small cell lung cancer.

Brigatinib was the focus of a 275-patient, multinational, phase III clinical trial called ALTA-1L whose results appeared in the New England Journal of Medicine in late September. At the same time, attendees at the International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer 2018 also heard the results.

Strong performance

They were impressive, said Dr. Ross Camidge, a medical oncologist at the University of Colorado Hospital and Joyce Zeff Chair in Lung Cancer Research at the CU Cancer Center. Camidge was lead author of the
ALTA- 1L study. The trial, Camidge said, pitted brigatinib against crizotinib, an older ALK inhibitor approved in the United States since 2011. In one key measure, study participants who received brigatinib had a 51 percent decreased risk of cancer progression or death compared with those who received crizotinib.

Camidge puts that number in perspective. “If you say as a patient, ‘What are my chances of my cancer not growing and my being alive at one year,’ it’s 87 percent for brigatinib and 43 percent for crizotinib.”

The trial results argue for brigatinib becoming the first-line treatment for lung cancer patients with the ALK mutation, Camidge said. He cited at least two key points for that conclusion. First, he noted that lung cancer has a tendency to metastasize to the brain in these patients.

“Crizotinib has a low penetration into the brain, and the cancer often remains essentially untreated,” Camidge said. In contrast, the study results show brigatinib had much greater success in “extending coverage to the whole body, including the brain,” he added. “We see with the data that this a very early differentiator between the two drugs.”

Apparent advantages

Camidge explained that in about half of the patients treated with crizotinib whose lung cancer had metastasized to the brain at the start of the study, the brain cancer progressed further within roughly five months. In patients with the same diagnosis treated with brigatinib, the percentage whose brain cancer progressed was much lower, said Camidge.

Dr. Ross Camidge of the UCHealth University of Colorado Cancer Center was lead author of the ALTA-1L study.
Dr. Ross Camidge was lead author of the ALTA-1L study.

Secondly, Camidge said, with just 10 months to a year of follow-up for patients in both of the treatment arms, researchers are “barely scratching the surface in terms of the difference” between the power of the two drugs to halt the progression of disease outside of the brain. He compared the ALTA-1L study results to a “movie trailer saying there is going to be really interesting stuff coming out of this when we start to see the full differential effects read out. “More mature data” should be available in about another year, Camidge said.

The reasons for brigatinib’s apparent advantage over crizotinib are partially but not completely understood, Camidge said. He noted that in some cases resistance to crizotinib occurs through the development of new mutations in ALK, while brigatinib still works on many of these. However, brigatinib may also possess an as-yet unidentified “secret sauce,” he added. That may be through effects on some other pathway in the cancer cell that enables brigatinib to achieve a longer period of control over the rogue cells emerging after crizotinib than any other ALK inhibitor. Understanding the basis of the “secret sauce” is the subject of further study, Camidge said.

Return to life

Sheri John only knows she’s gained the gift of time. Not satisfied with the original dismal prognosis in October 2016, her husband sought a second opinion, which led to an appointment with Dr. Tom Purcell, a medical oncologist and executive medical director of Cancer Services at UCHealth. Purcell and the lung cancer team identified John’s ALK mutation and enrolled her in the ALTA-1L trial. She began taking brigatinib just before Thanksgiving Day in 2016.

Two years later, John continues to take two pills containing the medication each night before bedtime. She said she’s had some minor side effects, including diarrhea that she controls with Imodium, and sometimes gets fatigued at the end of a long day. But those issues pale in comparison the benefits of the treatment.

“I feel great,” she said. “I work five days a week. I go to my agility classes and continue doing my regular stuff. I am active. I love the outdoors. I don’t sit around.”

As for the shortness of breath that presaged the cancer diagnosis, it is for now a thing of the past. “I can run the course in the agility ring again. Before, I couldn’t make it through, and I have no pain.”

A photo of Dr. Tom Purcell
Dr. Tom Purcell is encouraged by Sheri John’’s response to the brigatinib treatment.

Purcell views her progress with cautious optimism. “Sheri is an amazing person. She has tolerated the study medicine extremely well…and has had a complete response from her cancer. That means 100 percent reduction in her lung cancer,” he said in an email.

At the same time, Purcell acknowledged the adaptive power of the lung cancer John is fighting. “We are concerned about the cancer developing resistance,” he said. “Fortunately we have many options for treatment if that does occur.”

For her part, John calls Purcell “a godsend. I left the decision on my treatment up to Dr. Purcell to tell me what he thought would work best. The entire team at the Cancer Center is top-notch.”

She returns to the Cancer Center once a month for blood work and to get her medication, and receives imaging tests every 12 weeks. Otherwise, she lives her life as she always had before the illness. The unexceptional has become exceptional.

“I don’t know if I have a timeline,” John said. “My plan is to go on living life and not dwell on this. I feel like I have hope. I would like to just keep plugging away.”

About the author

Tyler Smith has been a health care writer, with a focus on hospitals, since 1996. He served as a writer and editor for the Marketing and Communications team at University of Colorado Hospital and UCHealth from 2007 to 2017. More recently, he has reported for and contributed stories to the University of Colorado School of Medicine, the Colorado School of Public Health and the Colorado Bioscience Association.