Lung Cancer: Killing Tumors Without Chemo--In-Depth Interview
Pasi Janne, MD, Director of the Lowe Center for Thoracic Oncology and Medical Oncologist at the Dana Farber Cancer Institute, talks about a new therapy that treats lung cancer.
What was the purpose of your trial?
Dr. Janne: The purpose of the trial was to evaluate whether a new targeted therapy was better than conventional treatment, which would be chemotherapy. The answer is yes, it’s much better; patients tolerate it better than chemotherapy and it’s moved in to being the standard of care treatment.
What exactly does the therapy do? Do you look at the DNA of the actual tumor itself to figure it out?
Dr. Janne: Patients have to have the specific molecular alteration. This is an alteration in a gene called ALK or anaplastic lymphoma kinase. It’s found in about 4 percent of lung cancer patients, so you have to have a test. You have to have a test to say you have this alteration or you don’t have this alteration. If you don’t have this alteration the drug is not going to work. If it is present, the trial showed it should work; patients were randomized to get the medicine first or the chemotherapy and as the trial showed it was better to get the medicine first.
How do you test for the alteration?
Dr. Janne: There is a test available both commercially and in pathology laboratories called a FISH test, or fluorescent in situ hybridization. It tests for where this genetic alteration happens; where a piece of chromosome has switched over on to its side, essentially. There are specific tests to look at the patient’s tumor to see if that’s taken place or not.
What are they looking for when they actually bring the tumor to the lab?
Dr. Janne: You’re looking at colored signals in the tumor. If this switching over has happened those signals, as opposed to being close together, have split apart now a little bit further. When those signals split apart a little bit further that genetic alteration has taken place.
What is the medicine most patients go on?
Dr. Janne: The medicine we are testing now is the next generation of an FDA approved drug Crizotinib. This is an oral medication, a pill. It’s a medicine they take by mouth twice a day; just like they would any other medicine. You take it every day. That’s very different than chemotherapy where you come to the clinic, you’re hooked up to an IV, you get the chemotherapy once a week or once every three weeks. The process of taking these two medicines is very different and so are the related side effects. The side effects of Crizotinib are relatively mild. People can take it on a day-to-day basis and essentially live normal lives.
What are some of the side effects?
Dr. Janne: There are some side effects; you can have some nausea, some mild side effects. There’s a kind of a unique visual side effect when patients go from dark to light they sometimes see this kind of flickering inside or at their periphery that goes away very quickly, and sometimes you can get some swelling in your legs. However, on balance it’s pretty good. It’s not like it makes you lose your hair, it doesn’t make you lose weight, and it doesn’t affect your blood cells to make you more susceptible to infections, unlike chemotherapy that can do all of those. You also can’t take chemotherapy indefinitely; you have cumulative side effects, numbness and tingling, fatigue, other things. Whereas, with medicines like Critzotinib, you can take as long as it’s working.
The patient could take it for the rest of their life?
Dr. Janne: If the cancer is kept at-bay. Now, unfortunately one of the things that we recognize is that even though we have these smart medicines and they’re great and they’re better than chemotherapy, they’re not curing people with advanced lung cancer. Ultimately, at some point these cancers do figure out ways to grow around the medicine. The really cutting edge of research happening right now is trying to figure out why that is the case. If we can understand why that’s the case, then we can develop better medicines or better combinations of medicines to make that benefit last even longer.
Just as the drug is not a cure, but keeps the cancer at bay, is chemo necessarily a cure or is it just the same situation?
Dr. Janne: No, it’s the same thing, just less effective. In the lung cancer field over the last several years there are now a few subsets of the disease where we have medicines that we use instead of chemotherapy. Again it’s the same reasons why they’re better: they’re better tolerated for a longer period of time. None of them are curative, but opposed to ten years ago where patients routinely would not live more than a year after being diagnosed with advanced lung cancer, many of these patients are living many years with their advanced lung cancer which is a great change. It gives us the enthusiasm and hope that as we study these more we’ll be able to make that duration even longer.
The studies show only 3 percent of the people that get stage four lung cancer would actually have the mutation?
Dr. Janne: Correct. Now it turns out that it’s not a random distribution of 3 percent, rather it tends to be in individuals who never smoked, which is about 15 percent of all lung cancers or individuals who have smoked very little. We now routinely test everybody for the mutation because we don’t want to miss anyone in that 33 percent. When we see patients at Dana Farber Cancer Institute for their first consultation we routinely send their tumors to be tested for ALK, as well as for a number of others to help choose the most appropriate therapy for them. It’s a paradigm shift as to how we treat lung cancer today, because it’s based on the genetics of their cancer.
Any other people who are more likely to have this genetic defect?
Dr. Janne: Younger patients are a little bit more likely to have it. Recently we did a study where we looked specifically at younger patients diagnosed with lung cancer; we defined younger as less than 40. The average age for lung cancer is in the late 60s if you look at national databases. However, occasionally we see younger patients that have the likelihood of having the ALK rearrangements, about 20 percent. It is higher than the 3 percent, so there are ways to try to enrich for that, but there are now also guidelines that have been put out by the pathology community that anybody with lung adenocarcinoma who walks in the door should have this test done and that’s happening routinely.
From a doctor’s point-of-view, when you looked at this study and you realized this is working and giving patients normal lives, how does it make you feel?
Dr. Janne: It’s amazing. It’s incredibly gratifying to see it with your own two eyes. Normally when you treat somebody who is symptomatic from their cancer, if you can’t treat them or don’t have a therapy their life expectancy is short. But if you find a medicine that is incredibly effective, like Crizotinib, and they essentially go back to normal or even go back to work, it’s incredibly gratifying. We’re fortunate that we’re seeing more and more of these examples today and hopefully there are many more to come.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
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