"The groundwork of all happiness is health." - Leigh Hunt

Surprising results of a lung cancer drug give patients hope

June 6, 2024 – Adam DeMara dismissed latest symptoms last fall – pain in the proper lower half of his body, shortness of breath while walking uphill on his golf course – as nothing to fret about, perhaps a hernia. But the symptoms remained.

“I took ibuprofen to help with the pain and then consulted a friend who is a doctor at Henry Ford Health,” said DeMara, 39, of Clinton Township, MI, who works on the health system as a clinical services representative.

After several tests, DeMara received a surprising diagnosis: he had a rare lung cancer that typically affects non-smokers and occurs at a much younger age than other lung cancers. It was stage IV non-small cell lung cancer brought on by mutations within the anaplastic lymphoma kinase (ALK) gene, or ALK-positive NSCLC.

While 85% of all lung cancers are non-small cell lung cancer (NSCLC), only 3% to five% of those cancers are ALK-positive. The prognosis is especially grim since the cancer often spreads to the brain and survival is often months. Worldwide, roughly 72,000 persons are diagnosed with ALK-positive NSCLC every year.

In DeMara's case, cancer has already been detected in each lungs, his liver, his bones and his brain.

His doctors prescribed him a targeted oral medication, lorlatinib (Lorbrena). The day before Thanksgiving, DeMara was literally couch-bound, but he began taking the drug. “After three or four days, I saw dramatic results,” he said. “I was still a little sick, but I was better, I was more mobile.”

In the months that followed, tests suggested that his tumors were either stable or shrinking. At his last doctor's appointment, he said, “there was a feeling of boundless optimism.”

His doctor, he said, seems to expect that he'll live for a very long time.

5-year results support lorlatinib

The results of a brand new 5-year follow-up study suggest that the optimism is justified study in a cancer journal and presented on the recent annual meeting of the American Society of Clinical Oncology in Chicago. In the Phase III clinical trial, CROWN, researchers randomly assigned 296 individuals with advanced and previously untreated ALK-positive lung cancer to receive either lorlatinib or crizotinib (Xalkori), one other targeted therapy for one of these cancer. Pfizer makes each drugs. DeMara was not a part of the study.

Lorlatinib improved progression-free survival and guarded the brain higher than crizotinib, replicating results from an earlier evaluation of the study.

For the 5-year follow-up, the researchers checked out a metric called median progression-free survival (PFS) – that's, how long a patient lives without the disease getting worse over the course of 5 years. While 60% of lorlatinib patients were still alive after 5 years without the disease getting worse, the figure for crizotinib patients was only 8%.

According to the researchers, progression-free survival in patients receiving lorlatinib was the longest ever recorded in a targeted molecular monotherapy for advanced NSCLC and for all solid tumors that had spread (so-called metastases).

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

“In the group that had no brain metastases firstly, [on lorlatinib] “We developed it over the next 5 years,” said Bauer, noting that spread to the brain was prevented by 96%. “The data are very strong and indicate good protection for the brains of our patients,” he said. The median time to brain progression was 16.4 months with crizotinib.

The drug blocks the ALK protein, slowing the expansion and spread of tumors. The FDA approved lorlatinib as a second- or third-line treatment in 2018 and as a first-line treatment in 2021.

Side effects, coverage

According to Pfizer, unwanted side effects may include numbness, fatigue, weight gain and joint pain. In the 5-year study, 5% of lorlatinib patients and 6% of crizotinib patients discontinued treatment as a result of unwanted side effects, and no latest questions of safety were identified.

“It makes your appetite go wild,” DeMara said. He quickly gained about 20 kilos, but his 6-foot-1 frame had grow to be too thin, he said. Now he can maintain his ideal weight of 220 kilos if he exercises rigorously.

Without insurance, the price could be greater than $7,000 a month. “Like most of our modern cancer drugs, it's very expensive,” Bauer said, “but fortunately insurance covers the cost for most patients.” There are also patient assistance programs, he said.

From incurable diagnosis to chronic illness?

Bauer, who consults for Pfizer, Bayer and Eli Lilly and Company, has diagnosed two patients with this rare cancer in recent months. He said he can now tell them: “We can treat your metastatic cancer with a pill that you take every day, which is usually well tolerated and can transform the disease into a chronic disease like heart disease or diabetes.”