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.


Taking Steps to Reduce Rates of Silica-Related Lung Cancer

Silica is a chemical found in sand and quartz and used in a multitude of industrial applications. Inhalation of silica dust can occur in a number of occupations and increases the risk of lung cancer. A recent review highlights new developments in understanding the health effects of silica exposure and recommends steps to reduce silica-related illness and death. Studies documenting the health risks associated with different levels of silica exposure have enabled evidence-driven regulations. Federal regulators are considering lowering the permissible occupational exposure to silica for workers, a measure that could cut the number of silica-related deaths in half. The review authors also recommend that workers exposed to silica who also smoke undergo computed tomography (CT) scans to screen for lung cancer starting at age 50 years.


FDA Mulls Change in Cancer Drug Approval Process

Modern cancer research indicates that cancers driven by genetic mutations in the same chemical pathway (a group of proteins in a cell that work together) may be more closely related, even if they occur in different parts of the body, than two cancers driven by different mutations that occur in the same organ. Current U.S. Food and Drug Administration (FDA) standards, however, still use the traditional anatomical location-based categories when approving cancer drugs (eg, lung cancer vs pancreatic cancer). As a result, a drug that is approved for treating a specific cancer caused by a given mutation must undergo new clinical trials to get approved for treating a cancer driven by the same mutation in another body part. However, the FDA’s ‘cancer czar’ recently floated an unofficial proposal for approving cancer drugs based on the chemical pathways they target. Such a change could greatly streamline cancer drug development.


FDA Mulls Change in Cancer Drug Approval Process

Modern cancer research indicates that cancers driven by genetic mutations in the same chemical pathway (a group of proteins in a cell that work together) may be more closely related, even if they occur in different parts of the body, than two cancers driven by different mutations that occur in the same organ. Current U.S. Food and Drug Administration (FDA) standards, however, still use the traditional anatomical location-based categories when approving cancer drugs (eg, lung cancer vs pancreatic cancer). As a result, a drug that is approved for treating a specific cancer caused by a given mutation must undergo new clinical trials to get approved for treating a cancer driven by the same mutation in another body part. However, the FDA’s ‘cancer czar’ recently floated an unofficial proposal for approving cancer drugs based on the chemical pathways they target. Such a change could greatly streamline cancer drug development.


FDA Mulls Change in Cancer Drug Approval Process

Modern cancer research indicates that cancers driven by genetic mutations in the same chemical pathway (a group of proteins in a cell that work together) may be more closely related, even if they occur in different parts of the body, than two cancers driven by different mutations that occur in the same organ. Current U.S. Food and Drug Administration (FDA) standards, however, still use the traditional anatomical location-based categories when approving cancer drugs (eg, lung cancer vs pancreatic cancer). As a result, a drug that is approved for treating a specific cancer caused by a given mutation must undergo new clinical trials to get approved for treating a cancer driven by the same mutation in another body part. However, the FDA’s ‘cancer czar’ recently floated an unofficial proposal for approving cancer drugs based on the chemical pathways they target. Such a change could greatly streamline cancer drug development.


FDA Grants Regular Approval to Xalkori for Treatment of ALK-Mutant Lung Cancer

The U.S Food and Drug Administration (FDA) has granted regular approval to the drug crizotinib (Xalkori) for the treatment of advanced non-small cell lung cancer (NSCLC) in patients who have mutations in the ALK gene. Xalkori received accelerated approval for this application in August 2011. Regular approval was awarded based on the results of a study examining patients with advanced NSCLC whose cancer had progressed despite first-line chemotherapy. Patients treated with Xalkori went an average of 7.7 months without further cancer worsening, compared to 3.0 months in those receiving the chemotherapy agents pemetrexed (Alimta) or docetaxel (Taxotere). Tumors shrank in 65% of the Xalkori-treated patients, compared to 20% with Alimta or Taxotere. However, overall survival did not differ between the Xalkori group and the chemotherapy group.


Compassionate Use of Unapproved Drugs Raises Difficult Ethical Issues

Patients with terminal illnesses, including late-stage cancer patients, are understandably eager to try still-unapproved experimental drugs once other options have been exhausted. The U.S. Food and Drug Administration (FDA) recently created a program to make it easier for drug companies to grant ‘compassionate use,’ which allows patients in extraordinary need access to otherwise unauthorized treatments. However, the decision to dispense experimental drugs is left to the companies, which are often reluctant to take this risky step. Experimental drugs are just that–experimental; they may have catastrophic side effects or simply not work. When these drugs are given outside the framework of a well-designed clinical trial, it becomes impossible to decisively judge whether they actually work. And if all patients could bypass clinical trials, there would be no incentive for anyone to enroll in these clinical trials, meaning that new drugs would never be properly studied and approved. Compassionate use therefore needs to be approved by experienced medical professionals on a case-by-case basis, and remain an option of last resort only.