The annual death rate from cancer has been steadily declining since it hit a high point in 1991. Improving diagnosis and the discovery of innovative therapies have contributed to the significant progress that has been seen during this period.

Another factor relates to the fact that the full therapeutic value of newly approved cancer therapies tends to be realized over time as clinicians become more familiar with their use and effectiveness. That also has the potential to lead to additional therapeutic indications for the therapy. A report, The Value of Innovation in Oncology: Recognizing Emerging Benefits Over Time, issued by Boston Healthcare Associates and commissioned by the Pharmaceutical Research and Manufacturers of America, delves into the reasons additional benefits of cancer therapies are revealed over time.

What the study found was that ongoing research and real-world application following their approvals often uncover greater benefit of new cancer therapies. The reason for that is that the complete clinical benefit of cancer medicines is often not entirely known at the time of initial FDA approval. Although a significant event, the approval, therefore, stands at the starting gate for what follows – an expanding knowledge base that eventually leads to the full value of the treatment and, more importantly, to help clinicians understand how best to use available therapies when treating their patients.

The study points out that this additional value often is recognized through a variety of pathways, some of which include use within a singular FDA-approved indication; use earlier in treatment line and in earlier disease stage; use in combination with other agents; and use in combination with specific biomarkers and companion diagnostics.

Cancer drugs approved under the FDA's accelerated approval program often will have to undergo continued studies to ensure safety and efficacy. In many cases, the report explains, that will lead to the accumulation of evidence that "may demonstrate even greater benefits."

One example is Xalkori (crizotinib, Pfizer Inc.), which was initially granted accelerated approval by the FDA in August 2011 for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) that is anaplastic lymphoma kinase-positive as detected by an FDA-approved diagnostic test. About two years later, the FDA revised the labeling to reflect the clinical benefit of Xalkori that had been revealed through ongoing studies.

It was also thought that the therapy could be effective in other forms of lung cancer. And so it proved. In April 2015, Xalkori was granted an FDA breakthrough therapy designation to potentially treat patients with ROS1-positive NSCLC, which occurs in about 1 percent of NSCLC cases. (See BioWorld Today, April 22, 2015.)

As the medicine chest for cancer drugs continues to grow, clinicians and researchers are discovering combinations of those drugs are proving an effective treatment strategy. The report describes an example with oral molecular targeted therapy Afinitor (everolimus, Novartis AG). That mTOR inhibitor was first approved by the FDA in 2009 for the treatment of advanced renal cell carcinoma.

Further research found that adding Afinitor to conventional chemotherapy plus anti-HER2 treatment reduced the risk of progression of HER2-positive advanced breast cancer resistant to Herceptin (trastuzumab, Roche AG) by 22 percent and may provide clues to the mechanisms underlying Herceptin resistance, researchers reported. (See BioWorld Today, June 4, 2014.)

Without that continuing research and collection of clinical evidence following the original approval of everolimus, those important additional benefits would not have been discovered, the report said.

Those pathways then "may provide a framework for a better understanding of the true clinical value of a therapy over time."