Our understanding of cancer has been morphing from a tissue-specific disease — think lung cancer or breast cancer — to a disease characterized more by specific genes or biomarkers than by location. A recent FDA decision underscores that transition and further opens the door to personalized medicine.
Two years ago, the director of the FDA’s Office of Hematology and Oncology Products told the Associated Press that there was no precedent for the agency to approve a drug aimed at treating tumors that generate a specific biomarker no matter where the cancer is in the body. Such a drug had long been seen as the epitome of personalized medicine. But with the rapid pace of progress in the field, director Dr. Richard Pazdur said, such an approval could one day be possible.
That day has arrived.
In a milestone decision for personalized medicine, the FDA approved Merck’s pembrolizumab (Keytruda) late last month for the treatment of tumors that express one of two biomarkers regardless of where in the body the tumors are located. The decision marks the first time FDA has approved a cancer drug for an indication based on the expression of specific biomarkers rather than the tumor’s location in the body.
Keytruda is designed to help the immune system recognize and destroy cancer cells by targeting a specific cellular pathway. The FDA notes that the two biomarkers — microsatellite instability-high (MSI-H) and mismatch repair deficient (dMMR) — affect the proper repair of DNA inside cells.
The approval represents an important first for the field of personalized medicine, which anticipates an era in which physicians use molecular tests to classify different forms of cancer based on the biomarkers they express, then choose the right treatment for it. In contrast to standard cancer treatments, which are given to large populations of patients even though only a fraction of them will benefit, Keytruda was approved only for the 4 percent of cancer patients whose tumors exhibit MSI-H or dMMR mutations. That may help the health system save money by focusing resources only on patients who are likely to benefit from Keytruda.
Such “personalized” strategies now dominate the landscape for cancer drug development. Personalized medicines account for nearly 1 of every 4 FDA approvals from 2014 to 2016, and the Tufts Center for the Study of Drug Development estimates that more than 70 percent of cancer drugs now in development are personalized medicines.
While this is encouraging, the U.S. research, regulatory, and reimbursement systems aren’t aligned to stimulate the development of personalized medicines, and may even deter progress.
The Trump administration’s proposal to cut biomedical research spending at the National Institutes of Health by 18 percent in fiscal year 2018, for example, would undermine its ability to fund more studies like the National Cancer Institute’s Molecular Analysis for Therapy Choice (MATCH) trial, which is designed to test targeted therapies across tumor types.
While the regulatory landscape for these targeted medicines is clear, the path to market for the molecular tests that do the targeting is not. That uncertainty continues to stifle investment in the innovative tests that make personalized medicine possible. The result is a clinical environment in which the patients who could benefit from personalized medicines are often never identified because the necessary tests aren’t available to them.
Finally, increasing pressure on pharmaceutical and diagnostic companies to decrease prices without considering their value to individual patients and the health system could also deter investment in innovative solutions that address unmet medical needs, particularly for smaller patient populations.
Confronted with unprecedented opportunities in personalized medicine, policymakers would do well to ensure that our research, regulatory, and reimbursement systems facilitate the development of and access to these promising new therapies. Only then can we ensure that Keytruda’s groundbreaking approval represents the beginning of a new era that promises better health and a more cost-effective health system.