Professor Dean Fennell, University of Leicester commented, “The launch of crizotinib heralds one of the most exciting breakthroughs that we have seen in cancer treatment in recent years. Up until now, patients with NSCLC have had few treatment options available to them. Crizotinib is the first treatment to target the ALK fusion protein specifically and as a result, patients expressing this fusion protein have a good chance of response. In other words, we know that we will be giving the right treatment to the right patient. Personalised medicines such as crizotinib represent the future of cancer treatment.”
The conditional licence for crizotinib is based on data from two multi-centre, single-arm studies, including a Phase 2 study and a Part 2 expansion cohort of a Phase I study. The primary endpoint in both studies was Objective Response Rate (ORR) (defined as complete response plus partial response), and ORRs of 50 percent and 61 percent were seen in the Phase 2 and Phase 1 studies respectively.
“Today’s news is a significant milestone for people with ALK-positive advanced NSCLC in the UK, “ said Dr David Montgomery, Medical Director, Pfizer Oncology UK. “Crizotinib is a new personalized treatment which offers the hope of better outcomes for people with this kind of lung cancer. It demonstrates Pfizer’s commitment to advancing the understanding of the underlying genetic drivers of diseases to help us to better identify people who are most likely to benefit from our treatments.
Pfizer will submit the results of a confirmatory phase 3 trial to regulators with a view to gaining a normal licence for the medicine. The phase 3 study, presented recently at the European Society for Medical Oncology (ESMO) 2012 annual congress, showed that in patients whose lung cancer is ALK-positive and whose cancer has progressed after first line chemotherapy, crizotinib provides superior tumour response, progression-free survival and quality of life compared to standard practice of second line single agent chemotherapy.
The global randomised phase 3 study of 347 patients with ALK-positive lung cancer showed that crizotinib more than doubled progression-free survival to a median of 7.7 months compared to 3.0 months among those patients who received the chemotherapy (HR 0.49; 95% CI 0.37–0.64 ; P<0 .0001). The overall response rate was also significantly higher in those treated with crizotinib (65% vs 20%; P<0.0001). These findings establish crizotinib as the standard of care for patients with previously treated advanced ALK positive NSCLC.
ALK is a newly identified therapeutic target in lung cancer. It is a protein expressed by cancer cells and is a direct and potent driver of the ALK positive variant of this disease. By inhibiting the ALK fusion protein, crizotinib blocks signalling in a number of cell pathways that are believed to be critical for the growth and survival of cancer cells. This can lead to growth inhibition or regression of cancers.
It is only possible to detect whether a tumour is ALK positive by performing laboratory tests on sample of a patient’s tumour tissue. For a patient to be eligible for crizotinib, their tumour must have tested positive for ALK using an accurate and validated test, undertaken by appropriately trained technicians with access to the required technology.
Lung cancer is the most common cause of cancer death in the UK, accounting for more than a fifth of all cancer deaths.Around 41,500 new cases of lung cancer are diagnosed in the UK every year.NSCLC accounts for about 85 percent of lung cancer cases and remains difficult-to-treat, particularly in the metastatic (or advanced) disease setting.Approximately 75 percent of NSCLC patients are diagnosed late with metastatic disease, where the five year survival rate is only one to five percent.Preliminary epidemiology suggests that approximately three to five percent of NSCLC tumours are ALK-positive.