An international clinical trial has shown that extending cancer testing beyond genetic mutations has potential to improve the personalized treatment of cancer.
In recent years, the field of precision medicine has been rapidly growing and is bringing a lot of hope to both patients and physicians, especially in the diagnosis and treatment of cancer. We have seen the approval of multiple drugs that aim to treat patients whose tumors carry specific genetic mutations, such as Roche’s Tarceva or Pfizer’s Xalkori. But the field is still young and so far only some cancer sufferers can benefit from these therapies.
Most precision medicine studies determine the best treatment based on mutations in tumor DNA, but not all tumors carry mutations that match with an available treatment. In a study published in Nature Medicine, the researchers added an extra step that looked at gene activation, which they measured by comparing RNA levels in tumors to those in healthy tissue.
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The trial was run by the Worldwide Innovative Network (WIN) consortium, a French non-profit that gathers cancer research centers across the world with the goal of improving the treatment of cancer.
The study recruited cancer patients across Spain, Israel, France, and Canada suffering from advanced forms of cancer that were previously unsuccessfully treated with several lines of therapy. Of the 303 patients that took part, 69 were matched to a treatment prescribed based on DNA mutations. Those patients that did not find a match based on their DNA went on to the RNA testing step, which resulted in 38 additional patients matched. In total, 35% of the patients could be prescribed a personalized approach.
“Previous studies have identified potential treatments for between 5% and 25% of patients based on DNA profiling alone, our findings represent an important step toward delivering on the true promise of precision medicine in oncology,” stated Richard Schilsky, Chairman of the WIN Consortium and CMO of the American Society of Clinical Oncology.
Despite showing promise, the trial failed to meet its initial goal of increasing by 50% the time patients had no cancer progression compared with the previous treatment they had received. However, the results did suggest that some patients might benefit more than others from a precision medicine approach. Those patients whose cancer did not cause physical restrictions and that had a high degree of match with the prescribed treatment survived for a median of 25.8 months, compared to 4.5 months for those that did not meet those criteria.
The study showed there is potential to expand the benefits of precision medicine to a larger number of patients. But it also highlighted there are multiple fronts where the field needs to keep advancing. A clear example was that most of the drugs given to patients were not approved for their form of cancer — out of the 159 different drugs included, 115 were prescribed off label, and 22 were still experimental therapies. As the field evolves, clinicians will have more solid evidence about how these treatments work in different forms of cancer.
Another of the challenges the researchers faced was that the testing methods used are not yet standardized in hospitals. In addition, one of the most common reasons the patients could not be matched was due to poor quality biopsies. In the future, these tests could be replaced by liquid biopsies, which can detect tumor mutations in traces of DNA found in the blood. Companies like Angle, Elypta or Inivata are striving to make this new technology the new standard in cancer testing.
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