Lorlatinib, which is already approved and available under the brand name Lorbrena in the United States, was tested in a clinical trial of hundreds of people with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC).
Roughly half received lorlatinib while the rest received crizotinib, an earlier generation drug.
After five years of follow-up, more than half of patients treated with lorlatinib did not see their cancer progress.
“We’re talking about patients with advanced metastatic disease — so this is actually a truly unprecedented finding,” Pfizer’s thoracic oncology strategy lead Despina Thomaidou told AFP.
Sixty percent of patients receiving lorlatinib, an oral one a day tablet, were alive without disease progression after five years compared to 8 percent on crizotinib.”There is an 81 percent reduction in the risk of progression or death,” added Thomaidou.Lung cancer is the leading cause of cancer deaths globally.
NSCLC accounts for more than 80 percent of lung cancers, with ALK-positive tumors responsible for roughly five percent of NSCLC cases, translating to around 72,000 new cases each year worldwide.
ALK-positive NSCLC mostly affects younger patients and is not strongly linked to smoking. It is also very aggressive — 25-40 percent of people with ALK-positive NSCLC develop brain metastases within the first two years.
Lorlatinib penetrates the blood-brain barrier better than prior generation medicines, said Thomaidou, and works to inhibit tumor mutations that drive resistance.
Patients on the lorlatinib arm had a 94 percent risk reduction in the progression of brain metastases compared to crizotinib.
Side effects of lorlatinib included swellings, weight gain and mental health problems such as depression.
“The progression-free survival is outstanding — we have not seen anything close to this,” said oncologist David Spigel of Sarah Cannon Research Institute in Nashville, who was not involved in the study.
One critique he had was that lorlatinib was compared to crizotinib, which was “an outstanding drug in its time,” but has since fallen out of use in the United States.
The results were published at the annual meeting of the American Society of Clinical Oncology and in the Journal of Clinical Oncology.
