A plain language summary of the 7-year results from the CROWN study: lorlatinib compared with crizotinib in people with ALK-positive non-small cell lung cancer

Plain Language SummaryWhat is this summary about?This is a summary of the results of a study called CROWN. The CROWN study included people with advanced non-small cell lung cancer (NSCLC) who had changes in a gene called anaplastic lymphoma kinase, or ALK, in their cancer cells. This type of cancer is called ALK-positive NSCLC. People participating in the study received a type of medicine, called an ALK inhibitor, as their first treatment. This study looked at the benefits of two ALK inhibitor medicines, called lorlatinib (also called Lorbrena/Lorviqua) and crizotinib (also called Xalkori), to understand if lorlatinib helped control the disease better than crizotinib. It also looked at side effects to determine the safety of the two medicines.When this study began in April 2017, crizotinib was the standard treatment for people with advanced ALK-positive NSCLC. This is why crizotinib was chosen as the medicine to compare with lorlatinib. This choice was discussed and agreed with regulatory agencies, such as the Food and Drug Administration (FDA). This analysis looked at how well lorlatinib and crizotinib worked and their side effects in people with advanced ALK-positive NSCLC after 7 years in this study.What are the key takeaways?In this study, 149 people took lorlatinib and 142 took crizotinib. All the people had advanced ALK-positive NSCLC. After observing people for 7 years, researchers found that more people who took lorlatinib were still alive without their cancer getting worse than people who took crizotinib. After 7 years, 66 out of 149 people (44%) were still taking lorlatinib, while only 4 out of 142 people (3%) were still taking crizotinib.After 7 years, people who took lorlatinib had a 55% estimated chance of being alive without their cancer getting worse, compared with a 3% estimated chance in people who took crizotinib. These results show how long people lived without their cancer getting worse; they do not show whether people who took lorlatinib lived longer overall. People who took lorlatinib and were alive without their cancer getting worse in the first 24 months of treatment had a 79% estimated chance of being alive without their disease getting worse after 7 years.The most common side effects in people who took lorlatinib were high levels of cholesterol and high levels of triglycerides (a type of fat) in the blood and edema (swelling). Between 5 and 7 years of treatment, none of the people taking lorlatinib had to stop taking it and not restart it to manage side effects. Everyone who stopped taking lorlatinib and did not restart it to manage side effects related to lorlatinib did so in the first 26 months of treatment. The types of side effects reported after 7 years and how often they happened were similar to the side effects reported after 5 years.What were the main conclusions reported by the researchers?The 7-year results from this study showed that more people who took lorlatinib continued to live longer without their cancer getting worse compared with people who took crizotinib. After being observed for an average of 7 years, more than half of the people who took lorlatinib are still alive without their cancer getting worse.Lorlatinib also showed long-lasting effects in the brain, with no new cancer growth observed in the brain after the first 30 months of treatment. This means that most people with advanced ALK-positive NSCLC who participated in this study were able to be treated with lorlatinib for a long time to keep their disease from getting worse or spreading to the brain. A summary of what the findings mean to the ALK-positive NSCLC patient community is included at the end of this plain language summary.Clinical trial number: NCT03052608