The results of two new lung cancer studies underscore Massachusetts General Hospital’s pioneering efforts in the field of targeted cancer therapy – or personalized medicine.
The new findings were published by physician-scientists from the MGH Center for Thoracic Cancers in two articles in a recent edition of The New England Journal of Medicine. Both papers present important developments in the use of crizotinib to treat non-small cell lung cancer. Crizotinib is a targeted cancer therapy drug that actively targets specific genetic mutations that stimulate cancer growth.
Cancer experts at the Mass General Cancer Center believe targeted cancer therapy will have a profund impact on the future of treatment. In December, Mass General opened the Henri and Belinda Termeer Center for Targeted Therapies. The new center aims to speed the discovery and delivery of new targeted cancer therapies by identifying specific genetic mutations that let tumors thrive. The targeted therapies are made to match these abnormalities, so they can attack the tumor on a molecular level. Such personalized medicine represents a significant shift in the focus of research and care. Instead of looking at the cancer based on location, scientists hone in on the genetics of each individual’s cancer cells to create a unique treatment plan.
Seeking Targeted Cancer Therapies with Fewer Side Effects
Non-small cell lung cancer, the subject of the new studies, is a devastating diagnosis, with a 5-year survival rate of only 15%. Chemotherapy is the foundation of treatment, but it can cause toxic side effects and offers only a 20-35% chance of tumor response. That situation has intensified the search for effective targeted therapies with fewer side effects. Because of work done at Mass General, crizotinib gained regulatory approval in 2011 for the treatment of ALK mutation-positive non-small cell lung cancer, and the drug is being considered as a therapy for ROS1 mutation driven cancers.
The first study involved a clinical trial directly comparing the impact of crizotinib to that of standard chemotherapy in treating ALK-positive tumors. For the trial, more than 300 patients with advanced ALK-positive non-small cell lung cancer were randomly assigned to receive either traditional chemotherapy or crizotinib.
Although development of resistance to targeted cancer therapies is common, the researchers sought to better understand the most effective therapeutic strategies moving forward.
The researchers from the MGH Center for Thoracic Cancer found that patients using crizotinib experienced significantly longer periods of progression-free survival, a higher response rate, and improved quality of life during treatment. “Hopefully, the results of this study will change clinical practice in the treatment of patients with advanced ALK-positive lung cancer and help further support access to crizotinib in many countries around the world,” said lead researcher Alice Shaw, MD, PhD.
A Discovery Highlights the Need for More Research
The second study analyzed resistance to crizotinib in ROS1-positive non-small cell lung cancer. Although development of resistance to targeted cancer therapies is common, the researchers, led by Dr. Shaw and Mass General’s Jeffrey Engelman, MD, PhD, sought to better understand the most effective therapeutic strategies moving forward.
The article presents a case study examining the first occurrence of resistance in a patient with a particular rearrangement of the ROS1 gene that has been shown to respond well to crizotinib. After an initially favorable response to crizotinib, the patient’s tumor quickly developed resistance and resumed growth.
The MGH researchers conducted a comprehensive molecular analysis of the tumor. It revealed a secondary genetic mutation in the initial ROS1 rearrangement that prohibits crizotinib from binding to the tumor cells.
Dr. Engelman hopes the discovery will lead to further research. “Finding that mutation at all sites of disease suggests that it was an early and critical event in the development of resistance,” he says. “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.”
Mass General manages the largest hospital-based research program in the United States, dedicating more than $775 million annually to research. Still, lung cancer research is severely underfunded. To learn more about how you can support the Center for Thoracic Cancers at Mass General, contact us.