New drug represents a ‘remarkable advancement’ in lung cancer


New data show that an unprecedented 60% of patients with advanced lung cancer given Lorbrena (lorlatinib) remain alive without disease progression after five years.

The trial results also demonstrated an 81% reduction in risk of progression or death and 94% reduction in progression of brain metastases compared to Xalkori (crizotinib).

The Phase III CROWN trial evaluated the third-generation ALK inhibitor in people with previously untreated, anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC).

Pfizer shared the results at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, which have also been published in the Journal of Clinical Oncology.

After five years of median follow-up, median progression-free survival (PFS) based on investigator assessment was not reached with lorlatinib, with an observed Hazard Ratio of 0.19, representing an 81% reduction in the rate of disease progression or death compared to crizotinib.

In addition, 60% of patients treated with lorlatinib were alive without disease progression after five years compared to 8% on the crizotinib treatment arm.

Significant progress in ALK-positive lung cancer

“ALK-positive advanced NSCLC is typically aggressive and often impacts younger people in the prime of their lives,” said Benjamin Solomon, Department of Medical Oncology, Peter MacCallum Cancer Centre, 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.”

In this updated analysis, lorlatinib showed a 94% reduction in the risk of developing intracranial (IC) progression. The median time to IC progression was not reached with lorlatinib and was 16.4 months with crizotinib.

In people without brain metastases at baseline receiving lorlatinib, only four of 114 developed brain metastases within the first 16 months of treatment, compared to 39 of 109 patients who received crizotinib.

At the time of analysis, 50% of patients in the CROWN trial were still receiving lorlatinib compared to 5% of patients receiving crizotinib.

“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, Director of Research and Clinical Affairs at the non-profit organisation ALK Positive. “These new results of the CROWN trial symbolise 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.”

Diana Spencer, Senior Digital Content Editor, DDW

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