Pfizer's LORBRENA® Study: Most ALK-Positive Advanced Lung Cancer Patients Survive Beyond Five Years Without Progression

Pfizer Inc. has shared significant updates from the Phase 3 CROWN trial, which investigates the efficacy of LORBRENA® (lorlatinib) compared to XALKORI® (crizotinib) in patients with untreated, ALK-positive advanced non-small cell lung cancer (NSCLC). The recent findings highlight the enduring benefits of LORBRENA, showing that 60% of patients remained alive without disease progression five years after treatment initiation, a remarkable outcome in this patient population.

The trial demonstrates that LORBRENA significantly reduces the risk of disease progression or death by 81% as compared to XALKORI, with a hazard ratio of 0.19. Additionally, LORBRENA was shown to reduce the risk of brain metastases progression by 94%. These results were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and published in the Journal of Clinical Oncology.

Roger Dansey, M.D., Chief Development Officer at Pfizer Oncology, emphasized the unprecedented nature of these results, attributing them to Pfizer’s commitment to innovative cancer treatment. He noted that the data supports LORBRENA as a standard first-line treatment for ALK-positive advanced NSCLC.

Lung cancer remains the leading cause of cancer-related deaths worldwide, with NSCLC accounting for 80-85% of lung cancer cases. ALK-positive tumors, which occur in approximately 3-5% of NSCLC cases, are often aggressive and can lead to brain metastases in 25-40% of patients within two years of diagnosis. LORBRENA was specifically developed to address resistance mutations and penetrate the blood-brain barrier, offering a strategic advantage in treating these patients.

Principal Investigator Benjamin Solomon, MBBS, Ph.D., highlighted the trial's significance, noting that the majority of patients treated with LORBRENA experienced long-term benefits, including protection against brain metastases. This marks a significant advancement in the treatment of ALK-positive NSCLC.

The updated analysis revealed that the median time to intracranial progression was not reached with LORBRENA, compared to 16.4 months with XALKORI. Among patients without initial brain metastases, only 4 out of 114 developed brain metastases within 16 months when treated with LORBRENA, whereas 39 out of 109 developed brain metastases on XALKORI. At analysis, 50% of patients were still on LORBRENA, compared to only 5% on XALKORI.

Kenneth Culver, M.D., Director of Research and Clinical Affairs at ALK Positive, a non-profit organization, noted the trial’s importance for the global patient community, emphasizing the substantial progress made in first-line targeted treatment for ALK-positive lung cancer.

Safety profiles in the five-year follow-up were consistent with previous findings. Common adverse events (≥20%) for patients on LORBRENA included edema, weight gain, peripheral neuropathy, cognitive and mood effects, diarrhea, dyspnea, arthralgia, hypertension, headache, cough, fever, high cholesterol, and high triglycerides. Grade 3/4 adverse events were more frequent with LORBRENA (77%) compared to XALKORI (57%), but treatment discontinuation rates due to adverse events were similar between the two drugs.

Pfizer continues to support patient and non-scientist understanding of these findings through accessible summaries. The CROWN trial involved 296 participants randomly assigned to either LORBRENA or XALKORI, with progression-free survival as the primary endpoint and several secondary endpoints, including overall survival and intracranial response.

LORBRENA is approved in the U.S. for treating adults with ALK-positive metastatic NSCLC. The safety and efficacy of LORBRENA continue to be underscored by its performance in long-term trials, offering hope and improved outcomes for patients facing this challenging diagnosis.