Trial Results For New Lung Cancer Drug Are ‘Off The Charts’
Researchers and oncologists are encouraged by the “unprecedented” and “off the chart” trial results for a new lung cancer drug that can potentially extend the lives of people diagnosed with the disease.
A recent study found the drug Lorlatinib improved survival rates by the longest time ever reported in people with advanced non-small cell lung cancer (NSCLC) caused by a mutation of the anaplastic lymphoma kinase (ALK) gene. ALK-positive lung cancers are aggressive and can spread to the brain. It’s estimated that up to 40 percent of people develop brain metastases within two years of being diagnosed.
The international research team conducting the CROWN study followed participants for five years and discovered that ALK-positive lung cancer did not progress in 60 percent of the participants who took Lorlatinib, compared to 8 percent of participants who took crizotinib, a standard drug used to treat the disease.
What’s more, in patients whose lung cancers had spread to the brain, Lorlatinib reduced the risk of their tumors progressing and helped prevent new brain metastases better than crizotinib.
Lorlatinib and crizotinib are both ALK tyrosine kinase inhibitors (TKI) that bind to the mutated ALK proteins to help stop the growth of tumor cells.
The CROWN study results were published in the Journal of Clinical Oncology and also announced at the American Society of Clinical Oncology’s (ASCO) annual meeting in Chicago in May.
According to Professor Benjamin Solomon of the Peter MacCallum Cancer Center in Melbourne, Australia, most patients treated with second-generation ALK-inhibitor drugs will see their disease progress within three years.
However, “the majority of patients taking Lorlatnib continue to have their disease controlled, including control of disease in the brain,” Solomon said in an ASCO news release. “To our knowledge, these results are unprecedented for any TKI in patients with metastatic NSCLC.”
Lung cancer (both small cell and non-small cell) is the second most common cancer in both men and women in the United States, according to the American Cancer Society (ACS). The ACS estimates a diagnosis of 234,580 new lung cancer cases and 120,070 lung cancer deaths in the United States in 2024. In addition, about 80 percent to 85 percent of all lung cancers are NSCLC, with ALK-positive tumors occurring in about 3 percent to 5 percent of NSCLC cases.
The National Institutes of Health report that people who have ALK-positive tumors tend to be younger than people with other forms of lung cancer and more likely to be light smokers or never have smoked.
Crizotinib, marketed as Xalkori, is considered a first-generation ALK inhibitor used to treat patients with ALK-positive tumors. Researchers designed Lorlatinib, a third-generation drug marketed as Lorbrena, to be effective against tumors that have stopped responding to first- and second-generation ALK inhibitors. Lorlatinib was also designed to cross the blood-brain barrier to help shrink tumors that have spread to the brain.
“You don’t need a magnifying glass to see the difference here,” Dr. Julie R. Gralow, ASCO’s chief medical officer, executive vice president, and press conference moderator, said during a briefing at the annual meeting. “It’s just a profound difference between these two drugs.
Dr. David Spigel, the chief scientific officer of the Sarah Cannon Research Institute in London, an oncology research organization that conducts community-based clinical trials for new cancer therapies, also praised the CROWN study outcomes.
“These long-term data results are off the chart, and this study confirms the outstanding durable efficacy of Lorlatinib as a first-line choice for patients with ALK-positive non-small-cell lung cancer,” Dr. Spigel said in a news release.
Dr. Spigel added that it is essential to compare Lorlatinib with other drugs, besides crizotinib, that treat ALK-positive lung cancer. Still, Dr. Spigel said the CROWN study findings are the “best outcomes ever observed for an ALK inhibitor.”
CROWN Trial’s Phase 3 Results
The third phase of the CROWN clinical trial involved 296 patients from 23 countries with previously untreated advanced forms of NSCLC. The participants were randomly assigned to receive either 100 mg of Lorlatinib once a day (149 participants) or 250 mg of crizotinib twice a day (147 participants).
About 59 percent of the study participants were women, and cancer had already spread to the brains of approximately 25 percent of participants when the study began.
Data for the five-year study was cut off on Oct. 31, 2023. At that point, the results showed:
- Over half of the participants who took Lorlatinib did not see a progression in their disease, while over half of the patients who took crizotinib experienced disease progression after just nine months.
- In patients who had brain metastases before the study began, the disease had progressed in only 8 percent of participants who took Lorlatinib and 79 percent in those who took crizotinib.
- Only four of the 144 participants who took Lorlatinib and did not have brain metastases when the study began developed brain metastases. The researchers wrote that this suggests that Lorlatinib can control and help prevent brain metastases.
- Side effects were more common in those who took Lorlatinib (77 percent) than in those who took crizotinib (57 percent). The most common side effects included swelling from fluid building up in tissues (edema), high cholesterol, and increased blood fat levels (hyperlipidemia).
While the CROWN study provided additional evidence on the effectiveness of Lorlatinib, Dr. Chen Zhao, a Stadtman investigator with the National Cancer Institute’s Center for Cancer Research, said a crucial question for both patients and healthcare providers is whether Lorlatinib or another ALK inhibitor, such as Alectinib, should be used as initial treatment for advanced ALK-positive NSCLC.
The answer will depend on several factors, Dr. Zhao said, such as a doctor’s previous experience with the drugs, whether the drugs are available, and a patient’s health insurance. He added that future studies comparing ALK inhibitors would also help answer the question.
Meanwhile, Dr. Solomon reflected on the “groundbreaking” results of the clinical trial and the advancements made in ALK medications since he began his medical training 20 years ago when most people diagnosed with ALK-positive lung cancer did not live more than a year.
“Now, we are seeing patients who are alive after 10-plus years, which is a great thing,” he said.
Source Links:
https://www.theguardian.com/society/article/2024/may/31/trial-results-for-new-lung-cancer-drug-are-off-the-charts-say-doctors?CMP=oth_b-aplnews_d-1
https://docwirenews.com/post/phase-3-crown-study-shows-longest-pfs-ever-reported-in-advanced-nsclc
https://society.asco.org/about-asco/press-center/news-releases/new-study-details-longest-progression-free-survival-ever
https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html
https://www.cancer.gov/news-events/cancer-currents-blog/2024/lorlatinib-alk-positive-lung-cancer-initial-treatment
