Lung Cancer Drug’s 'Off-the-Charts’ Results Give Patients Hope

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June 6, 2024 – Adam DeMara brushed off new symptoms last fall – feeling of pain in his lower right side, becoming breathless walking up a hill at his golf course – as nothing to worry about, maybe a hernia. But the symptoms persisted.

“I was taking ibuprofen to ease the pain, and then consulted with a friend who’s a doctor at Henry Ford Health,” said DeMara, 39, of Clinton Township, MI, who works at the health system as a clinic service representative.

After several tests, DeMara got the bombshell diagnosis: He had a rare lung cancer that typically affects nonsmokers, and at a much younger age than other lung cancers. It was stage IV non-small-cell lung cancer, involving mutations in the anaplastic lymphoma kinase (ALK) gene, or ALK-positive NSCLC.

While 85% of all lung cancers are non-small-cell (NSCLC), just 3% to 5% of the these cancers are the ALK-positive kind. The prognosis has been especially grim, as it's common for the cancer to spread to the brain and survival is typically measured in months. Globally, about 72,000 people a year get ALK-positive NSCLC.

In DeMara’s case, the cancer was already found in both lungs, his liver, bones, and brain.

His doctors prescribed a targeted oral medication, lorlatinib (Lorbrena). The day before Thanksgiving, DeMara was literally couch bound, but started the drug. “Within 3 or 4 days, I was starting to see dramatic results,” he said. “I was still a little bit sick, but I was better, more mobile.”

In the months since then, tests suggest his tumors are either stable or decreasing. At his last medical appointment, he said, “there was a feeling of ‘off-the-charts’ optimism.”

His doctor, he said, seems to think he is going to be living for a long time. 

5-Year Results Favor Lorlatinib

That optimism is warranted, suggest the results of a new 5-year follow-up study published in a cancer journal and presented at the recent American Society of Clinical Oncology annual meeting in Chicago. In the phase III CROWN clinical trial, researchers randomly assigned 296 people with advanced and previously untreated ALK-positive lung cancer to receive either lorlatinib or crizotinib (Xalkori), another targeted therapy for this type of cancer. Pfizer makes both medications. DeMara was not part of the study.

Lorlatinib improved progression-free survival and protected the brain better than crizotinib, repeating results of an earlier analysis of the trial.

For the 5-year follow-up, researchers looked at a measure called median progression-free survival (PFS) – how long a patient lives without the disease worsening over the 5 years. While 60% of the lorlatinib patients remained alive at 5 years without disease progression, just 8% of the crizotinib patients did.

The researchers said the progression-free survival for patients on lorlatinib was the longest ever reported with a single-agent molecular targeted treatment in advanced NSCLC and for all solid tumors that had spread, known as metastases.

Lorlatinib also provided strong brain protection, said Todd M. Bauer, MD, a principal investigator for the trial and a medical oncologist at Tennessee Oncology’s Greco-Hainsworth Centers for Research in Nashville. In the study, about 25% had seen the disease spread to the brain at the start of the study.

“In the group without brain metastases at the start, 4 of 114 [on lorlatinib] developed it over the next 5 years,” Bauer said, indicating a 96% prevention of spread to the brain. “It’s very strong data to suggest a good protective benefit for our patients’ brains,” he said. The median time to brain progression with crizotinib was 16.4 months.

The drug works by blocking the ALK protein, slowing the growth and spread of tumors. The FDA approved lorlatinib as second- or third-line treatment in 2018 and as first-line one in 2021.

Side Effects, Coverage

According to Pfizer, side effects can include numbness, fatigue, weight gain, and joint pain, among others. In the 5-year study, 5% of the lorlatinib patients and 6% of the crizotinib patients stopped treatment due to side effects, and no new safety issues were found.

“It makes the appetite ravenous,” DeMara said. He gained about 20 pounds quickly, but his 6-foot, 1-inch frame had gotten too thin, he said. Now, he’s been able to maintain at an ideal 220 pounds if he’s careful to exercise.

Costs without insurance may be more than $7,000 a month. “As with most of our modern anti-cancer drugs, it is very expensive,” Bauer said, “but fortunately, insurance does cover for most patients.” Patient assistance programs are also available, he said.

From Terminal Diagnosis to Chronic Disease?

Bauer, who consults for Pfizer, Bayer, and Eli Lilly and Company, has diagnosed two patients with this rare cancer in the past few months. He said he can now tell them: “We have the ability to treat your metastatic cancer with a pill you take every day that is typically well tolerated and can convert this disease into a chronic illness along the lines of heart disease or diabetes.”