First-line treatment with Lorbrena (lorlatinib) delayed disease progression at five years in more than half of people with ALK-positive metastatic non-small-cell lung cancer (NSCLC)—the longest progression-free survival ever reported for this type of cancer.

 

Lorbrena is a next-generation targeted therapy that interferes with ALK, a protein that plays a role in cell growth. Around 5% of people with NSCLC have ALK-positive tumors. Lorbrena was granted accelerated approval in 2018 and full approval in 2021.

 

The Phase III CROWN trial enrolled 296 patients with previously untreated Stage IIIb or IV ALK-positive NSCLC. They were randomly assigned to receive either oral Lorbrena once daily or the older ALK inhibitor Xalkori (crizotinib) twice daily.

 

In 2020, researchers reported that 78% of Lorbrena recipients were still alive without disease progression at one year, compared with 39% in the Xalkori group. Many participants were still doing well, so follow-up continued. After five years, progression-free survival rates were 60% versus 8%, respectively. The median progression-free survival time was 9.1 months in the Xalkori group but still has not been reached in the Lorbrena group. Lorbrena recipients had an 81% lower risk of disease progression or death and a 94% lower rate of disease progression in the brain. However, overall survival—the gold standard for clinical benefit—has not yet been reported.

 

These results “represent an unprecedented outcome for patients with advanced ALK-positive NSCLC and set a new benchmark for targeted therapies in cancer,” according to the study investigators.