The Chinese University of Hong Kong (CUHK)’s Faculty of Medicine (CU Medicine) co-led a landmark seven-year international Phase 3 clinical trial in lung cancer with multiple cancer centres worldwide. The study demonstrated that more than half of previously untreated patients with advanced ALK-positive non-small cell lung cancer (NSCLC) experienced no disease progression after receiving the third-generation targeted therapy lorlatinib as first-line treatment at seven years. This represents the longest progression-free survival (PFS) ever reported among targeted therapies for advanced solid tumours. The findings mark a significant step towards transforming specific oncogene-driven advanced lung cancer into a chronic condition, enabling patients to live with the disease long-term. The breakthrough results were presented by Professor Tony Mok, Chairman of the Department of Clinical Oncology at CU Medicine, at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in the leading international medical journal Annals of Oncology.

Lung cancer is the world’s most frequently diagnosed cancer and the top cause of cancer deaths, claiming an estimated 1.8 million lives each year. In Hong Kong, it is also the leading cause of cancer-related deaths, with more than 6,000 new cases diagnosed annually. NSCLC accounts for nearly 80% of all lung cancer cases, of which about 4% are ALK-positive. Brain metastases are highly prevalent among lung cancer patients, particularly those with ALK or EGFR gene mutations, affecting more than 30% of cases. Conventional radiotherapy offers limited efficacy in controlling brain metastases or achieving long-term survival.

Professor Tony Mok, Chairman of the Department of Clinical Oncology at CU Medicine, presented findings of the landmark seven-year international Phase 3 CROWN study at the 2026 American Society of Clinical Oncology Annual Meeting, which were simultaneously published in the leading international medical journal Annals of Oncology.

Unprecedented progression-free survival benefit

A total of 296 treatment-naive patients advanced ALK-positive NSCLC were enrolled in the global study and randomly assigned to one of two treatment groups. Of these, 149 patients received the third-generation targeted therapy lorlatinib, while 147 patients were given the first-generation agent crizotinib as the control. Findings are as follows:

Effectively prevents brain metastases and safe for long-term use

Brain metastases are one of the most common complications for patients with ALK-positive lung cancer, significantly impacting quality of life. Lorlatinib has demonstrated exceptional blood-brain barrier[1] penetration capabilities. No new cases of brain progression were observed after more than 30 months of treatment, and the rate of no new intracranial progression at seven years was as high as 92%, approximately six times higher than that of the control group.

Among patients with brain metastases at baseline, 83% stayed free of intracranial progression at seven years. Importantly, 96% of patients without brain metastases at the start of treatment did not develop intracranial progression over the seven years.  These findings suggest that lorlatinib provides substantial protection against the development of brain metastases.

Dr Molly Li Siu-ching, Assistant Professor in the Department of Clinical Oncology at CU Medicine, said, “Brain metastases significantly compromise both long-term survival and quality of life of lung cancer patients. These findings demonstrate that lorlatinib exerts a remarkable protective effect in both controlling existing brain tumour growth andmarkedly reducing the risk of new metastases. Notably, no intracranial progression was observed at 30 months of treatment. This sustained level of protection highlights its value as a preferred first-line option.”

The study also found that lorlatinib is safe for long-term use, with no evidence of new or more severe side effects. High cholesterol, high triglycerides, weight gain, and cognitive dysfunction are the most common adverse events which can be effectively managed through dose adjustments. Even when the dosage was reduced, the treatment’s therapeutic efficacy remained uncompromised.

Dr Molly Li Siu-ching, remarks that brain metastases significantly compromise both long-term survival and quality of life of lung cancer patients. The findings of this study demonstrate that lorlatinib exerts a remarkable protective effect in both controlling existing brain tumour growth and markedly reducing the risk of new metastases. Notably, no intracranial progression was observed at 30 months of treatment. 

A major step towards even more precise lung cancer treatment

The research team further analysed circulating tumour DNA  from patients’ blood samples and found that lorlatinib is able to suppress the emergence of new ALK mutations, thereby effectively preventing the development of treatment resistance, which is the key to its durable efficacy. Among the small proportion of patients who did develop resistance, it was primarily because the tumour found a “bypass” to activate other growth pathways.

Professor Tony Mok, Li Shu Fan Professor of Clinical Oncology, Associate Dean (Translation and Entrepreneurship) and Chairman, Department of Clinical Oncology at CU Medicine, who co-led the study, remarked: “The findings from this seven-year follow-up are unprecedented. Lorlatinib has demonstrated durable efficacy, significantly prolonging survival while enhancing quality of life through exceptional intracranial protection and drug safety. These results point to a real possibility of transforming advanced lung cancer from a terminal disease into a ‘chronic condition’,offering immense hope to lung cancer patients worldwide.”

A patient, Mr Ng, shares that he was diagnosed with advanced ALK-positive lung cancer in 2022 at the age of 58. He has been taking Lorlatinib for more than three years and already "considers himself free of the disease".