Gene testing identifies lung cancer patients who benefit from ALK-inhibitor drug

January 13, 2010

Results of a new study in non-small cell lung cancer showed that patients with specific oncogenic rearrangements of the anaplastic lymphoma kinase (ALK) gene within the short arm of chromosome 2 of their tumors had a much greater response to a new therapy - an ALK-inhibitor.

Findings were presented at the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer, held here from Jan. 11-14, 2010.

D. Ross Camidge, M.D., Ph.D., clinical director of the Thoracic Oncology Program at the University of Colorado, said this study and its results are an example of how all lung cancers are not created equal.

"This helps prove the principle that there may be many different molecularly defined diseases lurking under the same non-small cell lung cancer umbrella, each of which may derive considerable benefit from drugs that are highly specific to these molecular abnormalities if only we knew what they were. Here we have begun to move away from a one-size-fits-all treatment by testing lung cancers for specific in advance of choosing the treatment for them," Camidge said.

This study also represents a paradigm shift in cancer drug development as scientists now start to test their molecular hypotheses about which patients a targeted drug may or may not work on from the very first time the drug is tried out in humans, according to Camidge.

"If your hypothesis is right, the results can be dramatic and you could shave three to five years off the time from discovery to FDA approval by really focusing on who will benefit the most," he said. "This potentially means getting the right drug to the right patients far quicker than the oncology community has done previously."

Camidge and colleagues have been testing PF-02341066, a small molecule synthesized as an inhibitor of both ALK and cMET in a Phase I trial since 2006. The initial Phase I findings for this targeted drug were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, which was held in Orlando last June.

Study results presented at ASCO explored the initial determination of the appropriate dose of PF-02341066 in patients with all different types of cancers, followed by additional testing of the drug within the same study only in cancers proven to express markers of either ALK or cMET activation. In 2007, ALK gene rearrangements, which had previously been reported only in rare lymphomas, were reported in lung cancer and the study was amended to adapt to this emerging data.

Thus far, 31 ALK-positive lung cancer patients have been enrolled in the Phase I study. These patients were heavily treated; 65 percent received more than two prior treatment regimens. Patients with the ALK rearrangement had a 65 percent overall response rate, including 19 patients who had a partial response and one patient who had a complete response.

Patients remained on therapy for a median of 24 weeks, with many still on treatment. Accurate measurements of progression-free survival have not yet been reached.
Adverse events associated with PF-02341066 at the 250 mg twice-daily dose have been mild and include gastrointestinal and dark-light vision disturbances.

Exploration of the drug in cMET positive patients continues, but striking clinical responses in ALK-positive lung cancers have already been noted. On the basis of these results, a Phase III study of PF-02341066 in ALK-positive lung cancer compared to standard chemotherapy has now begun.

At this year's AACR-IASLC Joint Conference on Molecular Origins of Lung, Camidge will present updated data on ALK-positive patients treated with PF-02341066 and will explore the change in philosophy this trial represents in terms of modern cancer drug development.

Explore further: Viruses may play a role in lung cancer development

Related Stories

Viruses may play a role in lung cancer development

April 25, 2008

Papers presented at the 1st European Lung Cancer Conference, jointly organized by the European Society for Medical Oncology (ESMO) and the International Association for the Study of Lung Cancer (IASLC) in Geneva, Switzerland ...

Gene that causes childhood cancer neuroblastoma is found

August 25, 2008

Scientists have discovered gene mutations that are the main cause of the inherited version of the childhood cancer neuroblastoma. In addition, the researchers found that the same mutations play a significant role in high-risk ...

Novel 4-drug combination proves safe for lung cancer treatment

November 13, 2008

The four drug-combination of carboplatin and paclitaxel, with the targeted therapies bevacizumab (Avastin) and cetuximab (Erbitux), is safe and may improve survival for patients with advanced lung cancer, according to a cooperative ...

Iressa proves just as effective as chemotherapy for lung cancer

November 21, 2008

Gefitinib, also known as Iressa, the once-promising targeted therapy for the treatment of non-small cell lung cancer, has proven as effective as chemotherapy as a second-line therapy for the disease with far fewer side effects, ...

Recommended for you

How the finch changes its tune

August 3, 2015

Like top musicians, songbirds train from a young age to weed out errors and trim variability from their songs, ultimately becoming consistent and reliable performers. But as with human musicians, even the best are not machines. ...

Machine Translates Thoughts into Speech in Real Time

December 21, 2009

( -- By implanting an electrode into the brain of a person with locked-in syndrome, scientists have demonstrated how to wirelessly transmit neural signals to a speech synthesizer. The "thought-to-speech" process ...


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.