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A breakthrough study displaying crizotinib resistance in a ROS1-positive lung tumour demonstrates the need to develop further alternative therapies for patients with advanced lung cancer.

By Anonymous on Jun 3, 2013

Researchers at the Massachusetts General Hospital (MGH) Cancer Centre will publish this study relating to the crizotinib resistancein the New England Journal of Medicine so as to occur at the same time as the American Society of Clinical Oncology annual meeting.  This study involved a non-small cell lung cancer (NSCLC) patient that received chemotherapy after the preliminary genetic studies did not find any tumour-related mutations at that time.

But, as the cancer progressed, further testing revealed that crizotinib could treat her tumour. Initially, the patient’s tumour responded well to the treatment and a dramatic improvement could be seen after less than a week of therapy. However, after three months, the tumour began to grow again which gradually led to the patient’s death.

Previously, this resistance to crizotinib in ROS1 – positive NSCLC was unknown and further molecular analysis revealed that there was an additional mutation in this genetic arrangement. The researchers discovered that this new mutation interferes with the crizotinib binding to the ROS1 protein, thereby preventing the development of tumour growth inhibitions.

Senior author of this study and MD of the MGH Cancer Centre Jeffrey Engelman said, “Finding that mutation at all sites of disease suggests that it was an early and critical event in the development of resistance. A similar and highly resistant mutation also occurs in ALK-positive tumors treated with crizotinib, so finding therapies that can overcome this particular type of mutation will be very important.”       

Investigators at this Cancer Centre have also produced another study, in conjunction with this one that compared the use of crizotinib and standard chemotherapy in treating advanced lung cancer patients, for the first time. It was discovered that crizotinib went further than the average progression-free survival of 3 months with chemotherapy to 7.7 months.

This study utilised 347 patients who had advanced ALK-positive NSCLC and had finished their first-line treatment who received either oral crizotinib twice a day or standard chemotherapy once every three weeks.  The response rate with crizotinib was 65%, three times higher than the traditional treatment of chemotherapy. After some time 60% of the chemotherapy group also received the targeted drug and enhanced their likelihood of survival.

Lead investigator for this study Alice Shaw said, “This study shows that patients with advanced ALK-positive lung cancer respond better to crizotinib and for longer periods of time.”Equally important, patients treated with crizotinib report better symptom control and quality of life than those treated with chemotherapy.”

Both these studies indicate that further testing and research will enable a variety of targeted cancer therapies to be developed, in time.