Crizotinib Hits Bulls Eye for Subset of Lung Cancer Patients
Crizotinib Hits Bulls Eye for Subset of Lung Cancer Patients
Hello. It's Mark Kris from Memorial Sloan-Kettering Cancer Center in New York, and I'd like to review today the article published last week in The New England Journal of Medicine concerning the drug crizotinib. It was a great opportunity when, in 2007, investigators in Japan discovered that there is yet another driver oncogene in non-small-cell lung cancer, and that is a fusion gene of echinoderm microtubule-associated protein-like 4 (EML4) in the ALK (anaplastic lymphoma kinase) gene. It led to a constitutive activation of the ALK kinase. And as it turned out, drugs that were already in clinical trial, including the drug crizotinib, which was reported last week, effectively block that activated kinase. In a real first in drug development, once the connection was made by investigators at Massachusetts General Hospital that if you inhibited that activated kinase in patients whose tumors were driven by this fusion gene, you could bring about dramatic shrinkages. For the first time in a phase 1 trial, patients were enrolled with that specific fusion gene, and as the dramatic results were presented last week, nearly 90% of patients had some tumor shrinkage. In three quarters of the patients, that shrinkage lasted more than 6 months. Side effects were extremely tolerable with the twice daily oral administration schedule. Mild nausea was the only common side effect seen and was never truly treatment-limiting.
I think what is important about this is that it gives us another validated target in patients with lung adenocarcinoma. This fusion gene is found pretty much exclusively in lung adenocarcinoma. All we know today is that it's mutually exclusive from the epidermal growth factor receptor (EGFR) mutation also found in that disease. So, we now have nearly 10,000 more cases in the United States each year with a driver oncogene in adenocarcinoma of the lung that we have the opportunity to detect using a routinely available fluorescent in situ hybridization (FISH) test. Added to the 20,000 cases of EGFR mutation, an amazing 30,000 patients with adenocarcinoma of the lung each year will have 1 of these targetable mutations.
So, I urge you to use this as further justification for getting mutation testing up front. Test for the EGFR mutation; if the patient has that, they can be effectively treated with erlotinib, and if patients do not have the EGFR, then test them for the EML4 ALK translocation by the standard FISH test. At least now before the drug is approved, there are clinical trials available across the country.
Crizotinib is the name of the drug. I encourage you to go to the Pfizer Website if you have a patient who has this fusion gene. I think this gives a greater support once again to that idea that genotyping patients up front will allow you to target therapy, give a patient the best chance to have a dramatic result from a therapy with the fewest side effects and results that, on balance, far outstrip those of chemotherapy. Stay tuned for more developments like this.
Hello. It's Mark Kris from Memorial Sloan-Kettering Cancer Center in New York, and I'd like to review today the article published last week in The New England Journal of Medicine concerning the drug crizotinib. It was a great opportunity when, in 2007, investigators in Japan discovered that there is yet another driver oncogene in non-small-cell lung cancer, and that is a fusion gene of echinoderm microtubule-associated protein-like 4 (EML4) in the ALK (anaplastic lymphoma kinase) gene. It led to a constitutive activation of the ALK kinase. And as it turned out, drugs that were already in clinical trial, including the drug crizotinib, which was reported last week, effectively block that activated kinase. In a real first in drug development, once the connection was made by investigators at Massachusetts General Hospital that if you inhibited that activated kinase in patients whose tumors were driven by this fusion gene, you could bring about dramatic shrinkages. For the first time in a phase 1 trial, patients were enrolled with that specific fusion gene, and as the dramatic results were presented last week, nearly 90% of patients had some tumor shrinkage. In three quarters of the patients, that shrinkage lasted more than 6 months. Side effects were extremely tolerable with the twice daily oral administration schedule. Mild nausea was the only common side effect seen and was never truly treatment-limiting.
I think what is important about this is that it gives us another validated target in patients with lung adenocarcinoma. This fusion gene is found pretty much exclusively in lung adenocarcinoma. All we know today is that it's mutually exclusive from the epidermal growth factor receptor (EGFR) mutation also found in that disease. So, we now have nearly 10,000 more cases in the United States each year with a driver oncogene in adenocarcinoma of the lung that we have the opportunity to detect using a routinely available fluorescent in situ hybridization (FISH) test. Added to the 20,000 cases of EGFR mutation, an amazing 30,000 patients with adenocarcinoma of the lung each year will have 1 of these targetable mutations.
So, I urge you to use this as further justification for getting mutation testing up front. Test for the EGFR mutation; if the patient has that, they can be effectively treated with erlotinib, and if patients do not have the EGFR, then test them for the EML4 ALK translocation by the standard FISH test. At least now before the drug is approved, there are clinical trials available across the country.
Crizotinib is the name of the drug. I encourage you to go to the Pfizer Website if you have a patient who has this fusion gene. I think this gives a greater support once again to that idea that genotyping patients up front will allow you to target therapy, give a patient the best chance to have a dramatic result from a therapy with the fewest side effects and results that, on balance, far outstrip those of chemotherapy. Stay tuned for more developments like this.
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