LORBRENA (Pfizer’s lorlatinib) has delivered the longest progression-free survival (PFS) ever reported in advanced ALK-positive, non–small cell lung cancer (NSCLC). The company reported 60% of patients treated with LORBRENA were alive without disease progression after five years, according to data from the phase III CROWN trial data presented during the 2024 ASCO Annual Meeting (Abstract LBA8503). LORBRENA is FDA approved for adults with metastatic ALK-positive NSCLC, as detected by an FDA-approved test.
These data have just been published in the Journal of Clinical Oncology. The lead author is Benjamin J. Solomon, PhD of the Peter MacCallum Cancer Center in Melbourne.
Patients in CROWN received either Pfizer’s LORBRENA or XALKORI (crizotinib). Notably, after five years of follow-up, median progression free survival (PFS) has yet to be reached in the LORBRENA group. There was an 81% reduction in the rate of disease progression or death compared to XALKORI and while 60% of patients treated with LORBRENA were alive without disease progression after five years, that compared to only 8% on the XALKORI treatment arm. That finding coupled with prolonged intracranial efficacy, and absence of new safety signals sets a new bar.
“These results from the CROWN trial are unprecedented, as the majority of patients on LORBRENA are living beyond five years without disease progression,” said Roger Dansey, MD, chief development officer, oncology, Pfizer.
He added that the results, “…support LORBRENA as a standard of care for the first-line treatment of people with ALK-positive advanced NSCLC.”
NSCLC accounts for about 85% of lung cancer diagnoses. The cancer tends to occur in younger patients who are nonsmokers. ALK-positive cancers account for only about 5 percent of NSCLC diagnoses. But lung cancer is the most common cancer worldwide, and it causes the most deaths. NSCLC is the most common type of lung cancer in the U.S. alone, accounting for 81% of all lung cancer diagnoses.
ALK-positive lung cancer is also particularly deadly. About 25% of patients have brain metastasis within the first two years of being diagnosed.
“ALK-positive advanced NSCLC is typically aggressive and often impacts younger people in the prime of their lives,” said Benjamin Solomon, MBBS, PhD, department of medical oncology, Peter MacCallum Cancer Center, and Principal investigator of the CROWN trial.
“This updated analysis shows that LORBRENA helped patients live longer without disease progression, with the majority of patients experiencing sustained benefit for over five years, including nearly all patients having protection from progression of disease in the brain. These improvements in outcomes for patients with ALK-positive NSCLC represent a remarkable advancement in lung cancer,” he added.
In this analysis, LORBRENA also showed a 94% reduction in the risk of developing intracranial (IC) progression. The median time to IC progression was not reached with LORBRENA and was 16.4 months with XALKORI. At the time of analysis, 50% of patients in the CROWN trial were still receiving LORBRENA compared to 5% of patients receiving XALKORI.
“Although ALK-positive advanced NSCLC accounts for only approximately five percent of all NSCLC cases, this translates to 72,000 people who are diagnosed worldwide each year,” said Kenneth Culver, MD, director of research and clinical affairs at the non-profit organization ALK Positive.
