Development of Diagnostic Tests for Targeted Therapies Faces Multiple Challenges

Targeted therapies are treatments aimed at specific biomarkers, such as genetic mutations, or overexpressed proteins. Tests that detect the targeted biomarker are needed to determine whether a patient would benefit from the treatment. The FDA offers an approval pathway for such tests, so-called “companion diagnostics” (CoDx), which requires that the test be evaluated alongside the drug in clinical trials. However, testing laboratories can also develop their own tests. These “laboratory-developed tests” (LDTs) are not currently regulated by the FDA. Development of LDTs is therefore much cheaper and faster (making CoDx comparatively less economically viable), but provides less evidence that these test are indeed effective. Moreover, LDTs can be designed to test for many different biomarkers, thus making more efficient use of limited biopsy tissue, while CoDx usually only test for the one biomarker relevant for their companion drug. A recent article calls for test developers, pharmaceutical companies, insurers, and the FDA to collaborate in resolving these issues.


Development of Diagnostic Tests for Targeted Therapies Faces Multiple Challenges

Targeted therapies are treatments aimed at specific biomarkers, such as genetic mutations, or overexpressed proteins. Tests that detect the targeted biomarker are needed to determine whether a patient would benefit from the treatment. The FDA offers an approval pathway for such tests, so-called “companion diagnostics” (CoDx), which requires that the test be evaluated alongside the drug in clinical trials. However, testing laboratories can also develop their own tests. These “laboratory-developed tests” (LDTs) are not currently regulated by the FDA. Development of LDTs is therefore much cheaper and faster (making CoDx comparatively less economically viable), but provides less evidence that these test are indeed effective. Moreover, LDTs can be designed to test for many different biomarkers, thus making more efficient use of limited biopsy tissue, while CoDx usually only test for the one biomarker relevant for their companion drug. A recent article calls for test developers, pharmaceutical companies, insurers, and the FDA to collaborate in resolving these issues.


Development of Diagnostic Tests for Targeted Therapies Faces Multiple Challenges

Targeted therapies are treatments aimed at specific biomarkers, such as genetic mutations, or overexpressed proteins. Tests that detect the targeted biomarker are needed to determine whether a patient would benefit from the treatment. The FDA offers an approval pathway for such tests, so-called “companion diagnostics” (CoDx), which requires that the test be evaluated alongside the drug in clinical trials. However, testing laboratories can also develop their own tests. These “laboratory-developed tests” (LDTs) are not currently regulated by the FDA. Development of LDTs is therefore much cheaper and faster (making CoDx comparatively less economically viable), but provides less evidence that these test are indeed effective. Moreover, LDTs can be designed to test for many different biomarkers, thus making more efficient use of limited biopsy tissue, while CoDx usually only test for the one biomarker relevant for their companion drug. A recent article calls for test developers, pharmaceutical companies, insurers, and the FDA to collaborate in resolving these issues.


New Targeted Drugs May Offer Treatment for KRAS-Mutant Lung Cancer

Abnormalities in the KRAS gene are the most common mutations in lung cancer, especially in lung adenocarcinoma, a type of non-small cell lung cancer (NSCLC). However, no effective targeted therapy directed at KRAS has been found. Instead, researchers have begun to focus on blocking molecules “downstream” in the chain of chemical reactions through which KRAS affects the cell. Two such molecules are TBK1 and MEK. A recent study found that the drug CYT387 blocks TBK1. CYT387 reduced tumor growth in mice with KRAS-mutant lung adenocarcinoma. Also in mice, CYT387 and the MEK inhibitor AZD6244, given together, shrank aggressive lung tumors with mutations in both the KRAS and the TP53 gene. Researchers now hope to investigate the two drugs in people.


Local Radiotherapy May Allow Lung Cancer Patients to Stay on Xalkori Longer

Crizotinib (Xalkori) is effective for patients with non-small cell lung cancer (NSCLC) who have a mutation in the ALK gene, but their cancer usually develops resistance to the drug. However, this resistance may affect only part of the cancer, while the majority of the disease still responds to Xalkori. In such cases, localized radiation may be used to destroy the resistant part of the cancer (a technique dubbed ‘weeding the garden’) while patients continue to take Xalkori. In a small study, patients treated with this method could take Xalkori almost three times longer than those not eligible for the treatment. Longer times on Xalkori were associated with higher rates of 2-year survival. The average time without further relapse after the first radiation treatment was 5.5 months, and patients could be treated multiple times. Similar approaches may be effective with other targeted therapies.


New DNA Sequencing Machine Drastically Reduces Cost of Genetic Testing

Cheaper, faster DNA sequencing has already started to revolutionize medicine, including cancer medicine. Decoding the first human genome (a person’s entire genetic information) took 13 years and $3 billion. Since then, the price has dropped to around $10,000. (Cheaper DNA-testing services like “23andMe” only test a small fraction of the genome.) Now, a new sequencing machine has been released that can sequence an entire genome for just $1,000 within 24 hours. The device will enable more health care centers to offer genomic testing, a key component in personalized medicine. Testing the entire genome of a tumor sample, for example, can identify the individual mutation driving the cancer growth in a patient and guide the selection of targeted therapies directed at the specific mutation.


New DNA Sequencing Machine Drastically Reduces Cost of Genetic Testing

Cheaper, faster DNA sequencing has already started to revolutionize medicine, including cancer medicine. Decoding the first human genome (a person’s entire genetic information) took 13 years and $3 billion. Since then, the price has dropped to around $10,000. (Cheaper DNA-testing services like “23andMe” only test a small fraction of the genome.) Now, a new sequencing machine has been released that can sequence an entire genome for just $1,000 within 24 hours. The device will enable more health care centers to offer genomic testing, a key component in personalized medicine. Testing the entire genome of a tumor sample, for example, can identify the individual mutation driving the cancer growth in a patient and guide the selection of targeted therapies directed at the specific mutation.


Lung Cancer Drug Disappoints in 2 Late-Stage Trials

In a recent phase III clinical trial, the cancer drug dacomitinib was no more effective than a placebo at prolonging survival for patients with advanced non-small cell lung cancer (NSCLC) for whom standard therapy had failed. Like the targeted drugs erlotinib (Tarceva) and gefitinib (Iressa), dacomitinib blocks the protein EGFR, but it also inhibits a number of similar, related proteins. Another trial compared dacomitinib to Tarceva in NSCLC patients who had previously received at least one EGFR inhibitor. Dacomitinib did not increase time without cancer worsening compared to Tarceva. Results from a third phase III trial, which compares dacomitinib to Iressa in NSCLC patients with EGFR mutations, are expected next year.


New DNA Sequencing Machine Drastically Reduces Cost of Genetic Testing

Cheaper, faster DNA sequencing has already started to revolutionize medicine, including cancer medicine. Decoding the first human genome (a person’s entire genetic information) took 13 years and $3 billion. Since then, the price has dropped to around $10,000. (Cheaper DNA-testing services like “23andMe” only test a small fraction of the genome.) Now, a new sequencing machine has been released that can sequence an entire genome for just $1,000 within 24 hours. The device will enable more health care centers to offer genomic testing, a key component in personalized medicine. Testing the entire genome of a tumor sample, for example, can identify the individual mutation driving the cancer growth in a patient and guide the selection of targeted therapies directed at the specific mutation.