Targeted therapy boosts lung cancer outcomes

June 1, 2013 by Rob Levy

–Thousands of patients with an advanced form of lung cancer that carries a specific dysfunctional gene are likely to fare better if treated with a targeted therapy than with traditional chemotherapy, report Dana-Farber Cancer Institute researchers and a team of international collaborators.

In a trial involving patients with non-small cell lung cancer (NSCLC) whose harbored an abnormal ALK gene, those who received the oral drug crizotinib, which acts directly on ALK, went a median time of 7.7 months before their disease began to worsen, compared to 3 months for patients who received traditional chemotherapy. Patients treated with crizotinib also had a better quality of life than those treated with standard chemotherapy. The findings will be released as an advanced online publication by the New England Journal of Medicine on June 1.

"This study demonstrates the value of testing lung for an ALK rearrangement, and it underscores the potential of cancer genomics to target cancer treatments to each patient," says the study's senior author, Pasi A. Jänne, MD, PhD, who is the director of the Lowe Center for Thoracic Oncology of Dana-Farber. "ALK now becomes the second that we are able to successfully target in lung cancer with drugs other than chemotherapy." Lung cancers with the first such gene, , are now commonly treated with EGFR inhibitors before chemotherapy.

The lead author of the study is Alice Shaw, MD, PhD, of Massachusetts General Hospital.

NSCLC is the most common form of lung cancer, striking nearly 200,000 people in the U.S. each year. Although abnormal ALK is found in only about 5 percent of NSCLC cases, that translates into more than 5,000 new patients annually who could potentially benefit from crizotinib therapy, the study authors state.

The phase 3 trial described in the paper involved 347 with advanced or metastatic NSCLC who had already been treated with standard chemotherapy. The most common side effects associated with crizotinib therapy – visual disorders, gastrointestinal problems, elevated liver enzymes, and leg swelling – were generally mild, Jänne said, and are markedly different than the fatigue and hair loss associated with chemotherapy.

The abnormality in ALK that arises in is not, strictly speaking, a mutation (a change in the sequence of DNA within a gene). Rather, it results from a chromosomal rearrangement, in which the structure of a chromosome – the scaffolding of genetic material – is altered.

Crizotinib is a drug agent that takes aim at key enzymes within cells called kinases, which are often abnormal in cancer. Originally designed to block a kinase called MET, it was later discovered to target ALK as well. At the time, it wasn't known that ALK was sometimes abnormal in . The discovery that it is abnormal in a small percentage of NSCLCs led to its testing against the disease.

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

Related Stories

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 ...

Ganetespib shows potency against ALK-positive lung cancer and overcomes crizotinib resistance

March 26, 2013
A drug that indirectly impairs the function of several cancer-driving proteins, including anaplastic lymphoma kinase (ALK), may be an effective new treatment for patients with ALK—positive non-small cell lung cancer.

Study shows different approach after progression in non-small cell lung cancer patients

November 15, 2012
Right now, the best known treatment for patients with metastatic non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase gene rearrangements (ALK) or epidermal growth factor receptor mutations (EGFR) is crizotinib ...

Crizotinib reduces tumor size in patients with ALK positive lung cancer

September 6, 2012
Crizotinib is effective in shrinking tumors in patients with anaplastic lymphoma receptor tyrosine kinase (ALK) positive non-small cell lung cancer, a cancer commonly found in people who never smoked, and should be the standard ...

Study examines drug resistance in ALK positive lung cancer

January 19, 2012
Scientists from the University of Colorado Cancer Center have once again advanced the treatment of a specific kind of lung cancer. The team has documented how anaplastic lymphoma kinase (ALK) positive advanced non-small cell ...

Tumors with ALK rearrangements can harbor more mutations

April 22, 2013
The identification of potentially targetable kinase mutations has been an exciting advancement in lung cancer treatment. Although the mutations driving many lung carcinomas remain unknown, approximately 50 percent of lung ...

Recommended for you

Physical activity could combat fatigue, cognitive decline in cancer survivors

July 25, 2017
A new study indicates that cancer patients and survivors have a ready weapon against fatigue and "chemo brain": a brisk walk.

Breaking the genetic resistance of lung cancer and melanoma

July 25, 2017
Researchers from Monash University and the Memorial Sloan Kettering Cancer Center (MSKCC, New York) have discovered why some cancers – particularly lung cancer and melanoma – are able to quickly develop deadly resistance ...

New therapeutic approach for difficult-to-treat subtype of ovarian cancer identified

July 24, 2017
A potential new therapeutic strategy for a difficult-to-treat form of ovarian cancer has been discovered by Wistar scientists. The findings were published online in Nature Cell Biology.

Immune cells the missing ingredient in new bladder cancer treatment

July 24, 2017
New research offers a possible explanation for why a new type of cancer treatment hasn't been working as expected against bladder cancer.

Anti-cancer chemotherapeutic agent inhibits glioblastoma growth and radiation resistance

July 24, 2017
Glioblastoma is a primary brain tumor with dismal survival rates, even after treatment with surgery, chemotherapy and radiation. A small subpopulation of tumor cells—glioma stem cells—is responsible for glioblastoma's ...

No dye: Cancer patients' gray hair darkened on immune drugs

July 21, 2017
Cancer patients' gray hair unexpectedly turned youthfully dark while taking novel drugs, and it has doctors scratching their heads.

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.