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

Study finds melanoma biomarkers predicting checkpoint blocker response

July 18, 2018
Scientists at Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC) have identified biomarkers in melanoma that could help tailor immunotherapy treatments to maximize the benefits for patients while reducing the likelihood ...

Link found between bitter-taste sensitivity and cancer risk

July 18, 2018
High bitter-taste sensitivity is associated with a significantly increased risk of cancer in older British women, according to researchers who conducted a unique study of 5,500 women whose diet, lifestyle and health has been ...

Scientists discover a mechanism of drug resistance in breast and ovarian cancer

July 18, 2018
There is a highly sophisticated way to treat some breast and ovarian cancers—a class of drugs called PARP inhibitors, designed to exploit the very defects that make tumors with certain mutations especially deadly. Yet this ...

Research identifies new breast cancer therapeutic target

July 18, 2018
Research led by Suresh Alahari, Ph.D., Professor of Biochemistry and Molecular Biology at LSU Health New Orleans School of Medicine, has shown for the first time that a tiny piece of RNA deregulates energy metabolism, an ...

Cancer patients may experience delayed skin effects of anti-PD-1 therapy

July 18, 2018
Cancer patients receiving anti-PD-1 therapies who develop lesions, eczema, psoriasis, or other forms of auto-immune diseases affecting the skin may experience those adverse reactions on a delay—sometimes even after treatment ...

Early supper associated with lower risk of breast and prostate cancer

July 18, 2018
Having an early supper or leaving an interval of at least two hours before going to bed are both associated with a lower risk of breast and prostate cancer. Specifically, people who take their evening meal before 9 p.m. or ...

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.