Has Precision Oncology Been Over-Promised?
The idea of precision cancer therapies targeting a patient’s cancer genome may have been oversold, according to Vinay Prasad, an oncologist from the Oregon Health & Science University in Portland. Arguing against him was oncologist David Hyman from the Memorial Sloan Kettering Cancer Centre in New York. The pair faced off against each other at a Precision Oncology debate at the American Association for Cancer Research annual meeting in Chicago last week; their confrontation was reported by Science.
Gene targeted cancer treatments began in 1998, when the breast cancer drug Herceptin was granted approval in the US by the US Food and Drug Administration (FDA). In the time since then, the FDA has approved a further 30 cancer therapies that are targeted at a particular genome mutation. These treatments have helped to treat many patients since being brought to the market, but some critics are concerned that a genomics-based approach will not bring the benefits that many pharmaceutical companies are promising. In particular, there is an uncertainty about how many patients will actually benefit from these specialised therapies.
“When you look at all of the data, it’s a sobering picture,” Prasad said.
In contrast, Hyman pointed to the statistics of patients that qualify for such treatments. He said that at Sloan Kettering, they have tested more than 25,000 patient tumours and have matched 15% to one of the 31 FDA approved treatments. A further 10% were matched with a drug currently undergoing clinical trials, while another 10-15% could be treated by a drug that has been tested in animals, but not humans. Hyman also stated that these results were not unique to his institution, but that other cancer centres were reporting similar statistics.
The successes of projects like this have spurred the development of many more drugs hoping to treat cancer patients with specific mutations. Last year, the FDA approved an immunotherapy drug for any advanced solid tumours that demonstrate mutations within the DNA repair pathway, making it the first cancer treatment that is ‘blind’ to the tissue of origin. Hyman argued that this type of drug development, which doesn’t centre on the original location of the disease, is opening up treatments for a much wider range of patients than before.
Prasad did agree that the pool of potential patients was growing, but he argued that it did not mean that more patients were actually benefitting from these treatments. In a paper he published in JAMA Oncology last week, he reported that just 6.6% of patients taking these targeted drugs saw positive results, as the therapies only shrink tumours in some of those eligible. At AACR, Prasad continued to say that even drugs currently in development are only showing a response rate of 22%, a level that is equivalent to traditional chemotherapy.
The debate also touched on a recent federal decision to allow Medicare, a national healthcare insurance system in the US, to cover a tumour sequencing assay that tests for 324 known cancer genes. Prasad argued that this could lead to clinicians prescribing patients with drugs that match their mutations, but which have not been proven to work in the patient’s particular cancer.
Ultimately, the pair did not reach a consensus on the practicality and promise of precision oncology, although there were some points of agreement; Prasad was supportive of the work that Hyman and his team have been doing to generate evidence within the field, and Hyman agreed that work still needs to be done to fully realise the promise of precision oncology.