For the last decade or so, the emphasis in oncology has been so-called targeted therapy, in which drugs counteract particular genetic mutations that drive tumor growth. These were supposed to displace conventional chemotherapy, which tends to poison fast-growing cells, both cancerous and healthy ones, causing serious side effects.
Targeted therapy has had some great successes, particularly the leukemia drug Gleevec. But cancer cells, which tend to mutate rapidly, can develop resistance to the targeted therapies. And it is becoming more difficult to develop drugs for each narrow population of patients with a particular tumor mutation.
The PD-1 drugs are in a sense a return to a one-size-fits-all approach. And it might be harder for the tumor to become resistant to the immune system, which can adapt, than to a single drug.
In fact, what most excited researchers here this weekend was “the tail.” When researchers plot on a graph how many patients remain alive over time, the curves tend to drop to near zero for metastatic cancer. A successful drug slows the rate of decline, but eventually almost all patients die from the cancer.
But with Yervoy and, experts hope, with the PD-1 drugs, there appears to be fraction of patients who do not die of the disease, at least for a long time. The curve levels out in a plateau.
Dr. Sznol said that of five patients treated at Yale with the Bristol-Myers PD-1 blocker, nivolumab, two had no evidence of recurrence even two years after stopping the drug.
Over all, 133 melanoma patients at various clinics took nivolumab in the Phase 1 trial. Median survival was 16.8 months, with 62 percent of patients alive at one year and 43 percent alive after two years. There was no comparison group in the study, but with the existing melanoma drugs, about 24 to 33 percent of patients are alive after two years, Dr. Sznol said.
So if the immune system is so effective, why doesn’t it cure cancer on its own? One reason is that cancerous cells are the body’s own cells, though mutated, and might not be recognized by the immune system as foreign. Another is that the tumors act to suppress the immune system.
Much of the previous attempts at cancer immunotherapy have focused on the first problem — trying to train the immune system to recognize the tumor and attack it.
The PD-1 drugs tackle the second problem of immune system suppression. How many cancers this will work for is still unclear. Much of the early work has been in melanoma, which is known to be more susceptible than many other tumors to immune system attack. There are cases, though rare, in which the immune system vanquishes melanoma on its own.
What is encouraging doctors is that the drugs can shrink some lung cancer tumors, which have not been considered particularly susceptible to immune attack. There are sporadic reports of cases with other cancers as well, like colorectal cancer.
