Vinay Prasad in Nature:
Precision oncology promises to pair individuals with cancer with drugs that target the specific mutations in their tumour, in the hope of producing long-lasting remission and extending their survival. The basic idea is to use genetic testing to link patients with the drugs that will work best for them, irrespective of the tissue of origin of their tumour. Enthusiasm has been fuelled by reports of exceptional or super responders — individuals for whom experimental therapies seem to work spectacularly well. In one such example, an individual with metastatic bladder cancer showed a dramatic response to the drug everolimus1. Sequencing later revealed that the patient had a mutation that affects the mTOR pathway, which is the mechanism of action of everolimus. Yet despite the hype surrounding rare cases such as these, most people with cancer do not benefit from the precision strategy, nor has this approach been shown to improve outcomes in controlled studies. Precision oncology remains a hypothesis in need of verification.
Few patients benefit from precision oncology. Data from some 2,600 people enrolled in a sequencing programme at the MD Anderson Cancer Center in Houston, Texas, showed that just 6.4% were paired with a targeted drug for identified mutations2. Similarly, the Molecular Analysis for Therapy Choice (NCI-MATCH) trial at the US National Cancer Institute has enrolled 795 people who have relapsed solid tumours and lymphoma, but as of May 2016 it had only been able to pair 2% of patients with a targeted therapy. But being assigned such a therapy is not proof of benefit. When patients with diverse, relapsed cancers are given drugs based on biological markers, only around 30% respond at all, and the median progression-free survival is just 5.7 months4. Multiplying the percentage of patients receiving targeted therapies by this response rate, I estimate that precision oncology will benefit around 1.5% of patients with relapsed and refractory solid tumours.