Alectinib halts lung cancer growth more than a year longer than crizotinib

June 5, 2017, American Society of Clinical Oncology

Findings from a phase III clinical trial point to a more effective initial treatment for patients with ALK-positive non-small cell lung cancer (NSCLC). Compared to the current standard of care crizotinib (Xalkori), the newer ALK inhibitor alectinib (Alecensa) halted cancer growth for a median of 15 months longer and caused fewer severe side effects.

The study will be featured in a press briefing today and presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting.

"This is the first global study to compare alectinib with crizotinib in ALK-positive lung cancer and establishes alectinib as the new standard of care for initial treatment in this setting," said lead study author Alice T. Shaw, MD, PhD, Director of Thoracic Oncology at Massachusetts General Hospital Cancer Center in Boston, MA. "Alectinib was especially beneficial in controlling and preventing brain metastases, which can have a major impact on ' quality of life."

About 5% of NSCLCs are ALK-positive, meaning they have a genetic rearrangement where the ALK gene is fused with another gene. In the United States, about 12,500 people are diagnosed with ALK-positive NSCLC each year.

Crizotinib, the first medicine to specifically target ALK, was approved by the FDA in 2011. Although the majority of patients initially benefit from crizotinib, the cancer typically starts growing again within a year. Alectinib is a more potent, next-generation inhibitor of ALK. It was initially approved in 2015 for use in patients with advanced NSCLC that worsens despite crizotinib.

About the Study

In this open label clinical trial (ALEX), researchers randomly assigned 303 patients with stage IIIB or IV, ALK-positive NSCLC to receive alectinib or crizotinib. The patients had not received prior systemic therapy for advanced NSCLC.

Key Findings

Alectinib reduced the risk of cancer progression or death by 53% compared with crizotinib. Based on independent review, alectinib extended the median time to progression by about 15 months (median progression-free survival was 25.7 months with alectinib and 10.4 months with crizotinib).

"Nobody imagined it would be possible to delay advanced lung progression by this much. Most targeted therapies for are associated with a median progression-free survival of roughly 12 months," said Dr. Shaw.

While both treatments cross the blood-brain barrier, alectinib was more effective in preventing brain metastases than crizotinib, because it can better penetrate into the brain. At 12 months, the incidence of was much lower with alectinib than with crizotinib (9% vs. 41%).

Overall, severe side effects were less common with alectinib than with crizotinib, occurring in 41% vs. 50% of patients. The most common side effects of alectinib were fatigue, constipation, muscle aches, and swelling, whereas crizotinib caused gastrointestinal problems and liver enzyme abnormalities.

Next Steps

The researchers will continue to follow patients on this study to see if those treated with alectinib live longer than those treated with crizotinib. Meanwhile, several ongoing clinical trials are comparing other next-generation ALK inhibitors to in the first-line setting.

Explore further: FDA continues recent trend of approval with new second generation lung cancer treatment

More information: abstracts.asco.org/199/AbstView_199_185951.html

Related Stories

FDA continues recent trend of approval with new second generation lung cancer treatment

December 23, 2015
The International Association for the Study of Lung Cancer (IASLC) is once again gratified to see the approval of a new second-generation lung cancer treatment that can help many patients in their battle against the disease. ...

Ceritinib provides longer PFS than chemo in phIII trial of ALK rearranged lung cancer

October 9, 2016
Ceritinib provides longer progression-free survival than chemotherapy in crizotinib-pre-treated patients with non-small-cell lung cancer harbouring an ALK rearrangement, according to results of the phase III ASCEND-5 study ...

Identification of mutations causing lung cancer resistance leads to new treatment strategies

September 17, 2014
Two mutations that cause lung cancer resistance to the investigational ALK inhibitor alectinib were identified, and this information may help design new treatment regimens for patients with ALK-positive lung cancer, according ...

Brigatinib first to offer over 1-year control of ALK-positive lung cancer post-crizotinib

May 17, 2017
About 3-5 percent of lung cancers are caused by changes in the gene ALK. In 2011, the FDA granted accelerated approval for the drug crizotinib to target these ALK changes. However, two major problems have remained: Crizotinib ...

Phase III trial shows crizotinib superior to single-agent chemotherapy for ALK-positive lung cancer

September 30, 2012
The results of a new phase III trial show that crizotinib, a targeted therapy, is a more effective treatment than standard chemotherapy for patients with advanced, ALK-positive lung cancer, researchers said at the ESMO 2012 ...

Serial analysis of CTCs may provide biomarker predictive of NSCLC response to crizotinib

May 1, 2017
Among patients with non-small cell lung cancer (NSCLC) fueled by ALK gene alterations who were being treated with crizotinib (Xalkori), a decrease in the number of circulating tumor cells (CTCs) harboring increased copies ...

Recommended for you

These foods may up your odds for colon cancer

January 18, 2018
(HealthDay)—Chowing down on red meat, white bread and sugar-laden drinks might increase your long-term risk of colon cancer, a new study suggests.

The pill lowers ovarian cancer risk, even for smokers

January 18, 2018
(HealthDay)—It's known that use of the birth control pill is tied to lower odds for ovarian cancer, but new research shows the benefit extends to smokers or women who are obese.

Single blood test screens for eight cancer types

January 18, 2018
Johns Hopkins Kimmel Cancer Center researchers developed a single blood test that screens for eight common cancer types and helps identify the location of the cancer.

Researchers find a way to 'starve' cancer

January 18, 2018
Researchers at Vanderbilt University Medical Center (VUMC) have demonstrated for the first time that it is possible to starve a tumor and stop its growth with a newly discovered small compound that blocks uptake of the vital ...

How cancer metastasis happens: Researchers reveal a key mechanism

January 18, 2018
Cancer metastasis, the migration of cells from a primary tumor to form distant tumors in the body, can be triggered by a chronic leakage of DNA within tumor cells, according to a team led by Weill Cornell Medicine and Memorial ...

Modular gene enhancer promotes leukemia and regulates effectiveness of chemotherapy

January 18, 2018
Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.