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Return to Drug Shows Promise for Some Non-Small Cell Lung Cancer Patients Overview

More on Drug Shows Promise for Some Non-Small Cell Lung Cancer Patients

Research and Clinical Trials

Return to Drug Shows Promise for Some Non-Small Cell Lung Cancer Patients Overview

More on Drug Shows Promise for Some Non-Small Cell Lung Cancer Patients

Drug Shows Promise for Some Non-Small Cell Lung Cancer Patients

Results Presented at Annual Cancer Meeting; Part of Trend Toward "Personalized" Cancer Treatments

New York (Jul 21, 2010)

Doctor in scrubs examines chest x-ray

Five percent may not sound like much. But when talking about a new treatment with the potential to help five percent of the 215,000 people diagnosed with non-small cell lung cancer (NSCLC) each year in the United States – the most common cause of cancer-related death – that figure becomes more significant.

Five percent is the proportion of people with NSCLC whose lung cancer is fueled by a gene fusion that can now be targeted with a novel anti-cancer drug called crizotinib. At the 46th Annual Meeting of the American Society of Clinical Oncology (ASCO), held in early June in Chicago, researchers presented phase I clinical trial data demonstrating that 87 percent of patients with NSCLC who had this gene fusion responded to treatment with crizotinib, experiencing either tumor shrinkage or disease stabilization that lasted a median of six months.

Crizotinib is now under evaluation in later stage clinical trials. NewYork-Presbyterian Hospital is participating in these pivotal clinical trials at its Columbia University Medical Center campus, and both NewYork-Presbyterian/Columbia and NewYork-Presbyterian/Weill Cornell Medical Center are conducting research to develop and assess other novel targeted therapies for NSCLC.

How Crizotinib Works

Crizotinib (also known as PF-02341066) works by targeting the EML4-ALK fusion oncogene. This gene fusion promotes lung cancer cell growth by encoding the production of a tumor-specific protein called anaplastic lymphoma kinase, or ALK – an enzyme that is critical for the growth and development of cancer cells. Crizotinib, which is taken orally, works by inhibiting the ALK enzyme. Some 10,000 people are diagnosed with ALK-positive NSCLC each year in the U.S.

Balazs Halmos, M.D.
Balazs Halmos, M.D.

Most of the patients in the phase I study were non-smokers or ex-smokers with adenocarcinoma, and many had received multiple prior therapies. A phase III study is under way comparing crizotinib with pemetrexed or docetaxel as second-line therapy in patients with ALK-positive NSCLC. A separate phase II study, led by the manufacturer (Pfizer, Inc.), is also available for ALK-positive patients who are ineligible for the phase III study or who receive standard chemotherapy in the pivotal phase III study.

"This is a very nice design that guarantees that essentially all patients with the ALK abnormality can obtain access to this promising drug," said Balazs Halmos, M.D., who is leading both the phase II and III clinical trials at NewYork-Presbyterian/Columbia. (For more information and to inquire about eligibility for these studies, please contact 212-305-8615.)

Bryan J. Schneider, M.D.
Bryan J. Schneider, M.D.

"This drug is another step in the right direction toward personalized medicine. It is likely to get approved, and will give us another tool in our arsenal for treating patients with non-small cell lung cancer," added Bryan Schneider, M.D. "At the same time, there are still another 95 percent of patients with non-small cell lung cancer for whom better treatments are needed."

Drug Trials for Other Groups

For those patients, studies are evaluating drugs such as ARQ197, which inhibits c-MET – a tyrosine kinase implicated in cancer cell migration, invasion, and proliferation which may also play a role in the development of the resistance that most patients develop to EGFR inhibitors such as erlotinib (Tarceva®). In fact, NewYork-Presbyterian/Columbia investigators were one of the first to publish findings regarding the molecular basis of erlotinib resistance.

"Treatment with cMET inhibitors such as ARQ197 may be suitable for patients who develop resistance to erlotinib," noted Dr. Schneider. A phase II study presented at this year's ASCO Annual Meeting showed that adding ARQ197 to erlotinib extended progression-free survival by 32 percent in patients with locally advanced or metastatic NSCLC compared to treatment with erlotinib alone.

NewYork-Presbyterian/Weill Cornell investigators are seeking ways to determine which sub-groups of patients with NSCLC might benefit from COX2 inhibitors such as apricoxib by studying urinary PGE-M levels. PGE-M is a metabolite of eicosanoids produced by COX2. Patients who experience a 50 percent decline in urinary PGE-M levels following five days of apricoxib administration would be able to enter a study to see if this drug improves tumor response when combined with standard chemotherapy.

At NewYork-Presbyterian/Columbia, investigators are participating in clinical trials assessing the anti-angiogenic agents sorafenib (Nexavar®) and VEGF Trap (aflibercept) in patients with NSCLC, as well as a study of bevacizumab (Avastin®) plus chemotherapy in patients with resected lung cancer.

"We're aiming to become better able to determine which patients should receive particular chemotherapy agents, based on the molecular biology of their disease, and which patients may not benefit, sparing them from side effects," concluded Dr. Halmos. "We're also learning how to use old chemotherapy drugs in new ways. Our goal is to better tailor therapy for each patient."

Contributing faculty for this article:

Balazs Halmos, M.D. is an Assistant Attending Physician at NewYork-Presbyterian Hospital/Columbia University Medical Center and an Assistant Professor of Clinical Medicine in Hematology/Oncology at Columbia University College of Physicians and Surgeons.

Bryan Schneider, M.D. is an Assistant Attending Physician at NewYork-Presbyterian Hospital/Weill Cornell Medical Center and an Assistant Professor of Medicine at Weill Cornell Medical College.

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