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Testing identifies ALK mutation

In 2016, sudden onset back pain and a lingering cough convinced Colin to see a doctor for the first time in decades. The Australian, who relocated to Colorado with his American wife in 1995, dismissed the cough as the lingering aftereffect of a cold. The back pain, he thought, was a muscular strain from twisting and bending to get in a low-slung sports car. Then 57, he prided himself on being one of the few dentists he knew who did not suffer from career-related back pain.  

A diagnosis of metastatic non-small cell lung cancer shocked Colin, who never smoked. In addition to the primary tumor in his left lung, cancer had spread to the membrane surrounding his lungs, called the pleura. There was also a large tumor on his spine. The cancer was incurable, doctors said.

About 85 percent of lung cancer, the deadliest cancer, is classified as non-small cell lung cancer. Roughly 20 percent of those cases are nonsmokers, about 30,000 people annually in the United States. Non-smokers with lung cancer are typically diagnosed at a younger age than smokers.

Colin needed immediate treatment. His doctor recommended chemotherapy, the standard protocol in 2016. As Colin researched chemotherapy side effects, he learned the median survival rate for his type of cancer was two years. He realized that meant his time could be as short as six months to a year.  Based on his reading and the symptoms he was experiencing, he expected those to be rough months.

Colin also read articles that reported that some lung cancer patients experienced promising results with a treatment called immunotherapy, which boosts the ability of a patient’s own immune system to combat cancer. That is the treatment he told his doctor he wanted.

But after two infusions, Colin and his doctor began to think the effects of immunotherapy might speed up his demise.

A month into treatment, scans showed the lung tumor had doubled in size and was impinging on a nerve, stealing his voice. Meanwhile, his horrific back pain and unrelenting cough continued unabated, preventing sleep. He had an itchy rash all over his body, a reaction to the immunotherapy. He had to stand to eat because it was too painful to sit. And it was too painful to lie down to sleep.

“My quality of life was dreadful, and I figured I didn’t have much time left,” he said. “I took comfort knowing that my son was grown and my wife, an independent person, would not struggle financially.”

 Then, unexpectedly, there was a glimmer of hope.

Colin’s oncologist called with what she said was exciting news: A sample of one of his tumors taken during a biopsy had been sent to a laboratory for genetic sequencing to determine whether its growth was being driven by a genetic mutation, which is a change in his DNA. The test results showed his tumor had an ALK (short for anaplastic lymphoma kinase) mutation, a fusion of the ALK gene and another gene, which causes cells to grow out of control. Further testing revealed the tumor might respond to a drug that inhibits the runaway growth of ALK-driven cells.

“None of those words meant anything to me at that time,” Colin recalled. “I wasn’t even aware that they were conducting the genetic tests on my tumor.”

Advancements in next-generation sequencing fuel precision medicine

In 2016, using next-generation sequencing (NGS) to identify cancer-driving mutations in patient tumors was in its infancy. So too were companion diagnostics (CDx) that are used to test for biomarkers, a type of biological flag on a cell, that indicates whether a particular drug can target the havoc caused by the cancer’s genetic mutation.

Although not widely adopted, the tests were most frequently used on lung cancer because multiple genetic mutations were linked to the disease. The testing was primarily conducted at large cancer centers equipped with all the necessary equipment and expertise, not at community clinics, where the majority of the world’s cancer patients receive treatment.

However, the community clinic that treated Colin sent the tissue from his biopsy to a commercial laboratory that could perform NGS. The results were returned after several weeks. For Colin, it was not too late to change his treatment.

His doctor prescribed an oral medication called crizotinib, known as a targeted therapy, it inhibits the results of the ALK mutation. It was the first ALK inhibitor approved by the U.S. Food and Drug Administration and had been shown to buy patients about 4 months before the disease progressed.

But Colin’s condition continued to worsen. Tests showed life-threatening liver damage. He soon needed supplemental oxygen at night and when walking. He also needed to use a walking stick.   

Colin’s doctor then switched him to a second-generation ALK inhibitor, alectinib, hoping it would have less severe side effects. The new drug had the added benefit of being able to penetrate the blood-brain barrier, which prevents many substances from entering the brain. Non-small cell lung cancer often metastasizes to the brain, so Colin needed that protection. Studies have shown patients live a median of 35 months on alectinib before their cancer progresses.

Within a few weeks, Colin began to feel better. After about two months, his scans showed the cancer in his spine and pleura was mostly gone, although permanent damage was evident. Only a small area of residual tumor remained in his lung, and it has remained relatively stable.

“It was easy to understand why many people refer to these targeted therapies as miracle treatments,” Colin said.