Drug trial results show lung cancer patients are living longer

Pfizer has announced promising follow-up results from its Phase 3 CROWN trial evaluating LORBRENA (lorlatinib, a third-generation ALK inhibitor) in 296 people with previously untreated, anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC).

Lung cancer is the number one cause of cancer-related death and NSCLC accounts for 80–85% of lung cancers, with ALK-positive tumours occurring in about 3–5% of NSCLC cases. 25–40% of people with ALK-positive advanced NSCLC may develop brain metastases within two years from initial diagnosis. LORBRENA was specifically developed by Pfizer to inhibit tumour mutations that drive resistance to other ALK inhibitors and to penetrate the blood–brain barrier.

Participants in the Phase 3 CROWN trial were randomised to receive either lorlatinib or an earlier treatment, crizotinib (XALKORI). As median progression-free survival (PFS) was not reached after three years of follow-up, an unplanned post hoc analysis was executed with the intent to further quantify long-term outcomes at five years. The international clinical trial was led by Melbourne’s Peter MacCallum Cancer Centre (Peter Mac).

Five years after treatment, 60% of patients treated with lorlatinib remained alive and without disease progression; this compared to just 8% for patients who received crizotinib. The updated results also show an 81% reduction of risk of progression or death, and 94% reduction in progression of brain metastasis, compared to crizotinib. These results were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, as well as being published in the Journal of Clinical Oncology.

“These results from the CROWN trial are unprecedented, as the majority of patients on LORBRENA are living beyond five years without disease progression,” said Dr Roger Dansey, Chief Development Officer, Oncology, Pfizer. “These results are an excellent example of Pfizer’s longstanding 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.”

“ALK-positive advanced NSCLC is typically aggressive and often impacts younger people in the prime of their lives,” said Peter Mac’s Professor Ben Solomon, principal investigator for the CROWN trial. “This updated analysis shows that lorlatinib 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.”

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