Pfizer’s LORBRENA achieves 60% five-year survival in ALK-positive lung cancer

Phase 3 CROWN trial shows 81% reduction in progression risk and 94% fewer brain metastases compared to XALKORI®

New Delhi: Pfizer Inc. has announced that longer-term follow-up results from the Phase 3 CROWN trial demonstrate unprecedented outcomes for LORBRENA® (lorlatinib) in treating ALK-positive advanced non-small cell lung cancer (NSCLC).
After five years, 60% of patients remain alive without disease progression, showcasing a significant improvement over the previous standard treatment with XALKORI® (crizotinib).
The trial’s median follow-up period revealed that the median progression-free survival (PFS) was not reached with LORBRENA. The results showed an 81% reduction in the rate of disease progression or death compared to XALKORI, with a Hazard Ratio (HR) of 0.19 (95% Confidence Interval [CI], 0.13-0.27). Specifically, 60% of patients treated with LORBRENA (95% CI, 51-68) were alive without disease progression after five years, compared to just 8% (3-14) of patients on XALKORI.
“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, M.D., Chief Development Officer, Oncology, Pfizer. “These results are an excellent example of Pfizer’s long-standing commitment to discovering and developing scientific breakthroughs for patients, and support LORBRENA as a standard of care for the first-line treatment of people with ALK-positive advanced NSCLC.”
The updated analysis presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and published in the Journal of Clinical Oncology, also revealed a remarkable 94% reduction in the risk of developing brain metastases with LORBRENA (HR, 0.06; 95% CI, 0.03-0.12). The median time to intracranial (IC) progression was not reached with LORBRENA but was 16.4 months with XALKORI. Among patients without brain metastases at the start of treatment, only 4 out of 114 developed brain metastases within the first 16 months on LORBRENA, compared to 39 out of 109 on XALKORI.
Dr. Benjamin Solomon, MBBS, Ph.D., of the Peter MacCallum Cancer Centre and Principal Investigator of the CROWN trial, emphasized, “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.”
Lung cancer remains the leading cause of cancer-related deaths worldwide, with an estimated 234,580 new cases expected to be diagnosed in the U.S. in 2024. Non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of these cases. Among NSCLC patients, 3-5% have ALK-positive tumors, which are particularly aggressive and often affect younger individuals. 
“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, M.D., Director of Research and Clinical Affairs at the non-profit organization ALK Positive. “These new results of the CROWN trial symbolize significant progress in the first-line setting for the targeted treatment of ALK-positive lung cancer, which has led to notable improvements for the patient community.”
Safety profiles for LORBRENA and XALKORI in the five-year follow-up remained consistent with previous findings. The most frequent adverse events (AEs) for LORBRENA included edema, weight gain, peripheral neuropathy, and cognitive effects. Grade 3/4 AEs occurred in 77% of patients with LORBRENA and 57% with XALKORI, with treatment-related AEs leading to discontinuation in 5% of LORBRENA patients.