Lung cancer patients with a specific genetic alteration improve their life expectancy and eliminate the risk of brain metastasis when treated early with the drug lorlatinib. A study led by researchers from the Hospital General de Massachusetts (MGH), published in (NEJM).
Non-small cell lung cancer (NSCLC) represents the 87% of all lung cancer cases. About 5% of NSCLC cases are ALK positive, which means they have a genetic abnormality in the anaplastic lymphoma kinase gene. The NSCLC ALK positive, which is not associated with smoking, is a particularly aggressive form of lung cancer.
“When ALK is turned on abnormally, it’s like stepping on the gas: it drives the uncontrolled proliferation and survival of cancer cells,” explains researcher Alice Shaw.
Specifically, ALK positive patients tend to be 10-15 years younger than other lung cancer patients. They also have a high risk of developing brain metastases.
In 2008, a new class of drugs that block ALK was discovered, known as ALK inhibitors. “Turning off ALK with an ALK inhibitor is like braking,” reveals Justin Gainor, “It can lead to the rapid death of cancer cells and cause tumors to shrink dramatically.”
There are first and second generation ALK inhibitors, including crizotinib, alectinib, and brigatinib, which can be very effective, but patients relapse. Also, those treated with these drugs can develop metastatic spread of cancer to the brain.
Lorlatinib belongs to a third generation of this class of drugs and is even more effective in blocking ALK. It is currently approved by the US Food and Drug Administration. (FDA) and in Europe for the treatment of ALK positive patients whose cancer has progressed despite taking ALK inhibitors from previous generations.
The research, carried out in 104 medical centers in 23 countries, recruited 296 patients with NSCLC ALK-Advanced positive that had not been previously treated. Half received lorlatinib, while the rest were treated with crizotinib, which was the standard treatment for these patients when the trial began.
The results were amazing. Compared with those who received crizotinib, those in the lorlatinib group had a 72% reduction in the risk of cancer progression or death.
Importantly, lorlatinib it also decreased the risk of brain metastases new or recurring by 93%. Serious side effects were more common in the lorlatinib group, but more than half were increases in blood cholesterol and triglyceride levels, which were manageable with medication.