Many promising studies presented at the 2013 American Society of Clinical Oncology (ASCO) annual meeting involved new cancer drugs that empower the body’s defense system. Although most are still in early testing, the drugs are thought to work by unleashing the immune system to attack cancer cells and could be an alternative to often-debilitating chemotherapy. The new drugs disable a brake on the immune system called the programmed death 1 receptor, or PD-1.
Although the data presented at the meeting were from the earliest state of testing, the drugs were the center of attention in June, with some researchers predicting that cancer treatment had hit a milestone and was about to experience a major shift toward immunotherapy. Some analysts predicted that the drugs could reach market in as early as 2015.
According to the researchers, harnessing the immune system is appealing for several reasons.
- It might be applicable to many different types of cancer.
- It could produce longer-lasting remissions than can be achieved by chemotherapy or the current targeted drugs.
- It might seem more natural and holistic than chemotherapy drugs to some people.
One drug presented was Merck’s experimental PD-1 inhibitor, lambrolizumab, which has been shown promising results in a melanoma trial since January 2012. However, the findings of studies of this and other drugs presented at ASCO should be interpreted with caution. Many other hoped-for miracles have failed to materialize, and this is a conference where drugs that extend lives by only a few weeks are viewed as breakthroughs.
PD-1 inhibitors have been shown to shrink tumors significantly in 15%–50% of patients, although it has not been clearly established that the drugs increase survival. In addition, the results seen in trials, which are conducted under idealized conditions, do not translate perfectly to the real world.
One poster presented the use of ipilimumab, a melanoma drug approved in 2011 that disables a different immune system brake. Median survival in recent studies has been only about half of what was seen in clinical trials. Moreover, just because the immune system is involved does not make something safe. Ipilimumab has some serious side effects caused by overstimulation of the immune system, including lung inflammation, which was seen in some patients.
Since the early 2000s, cancer research has centered on targeted therapies, in which drugs counteract particular genetic mutations that drive tumor growth. These drugs were suppose to replace traditional chemotherapy and its serious side effects. But cancer cells multiply rapidly and can develop resistance to targeted therapies. In addition, it proved difficult to develop drugs for each narrow population of patients with a particular tumor mutation.
The PD-1 drugs are a return to a one-size-fits-all approach, where it might be harder for a tumor to become resistant to the immune system, which can adapt, than to a single drug. But how many cancers this type of treatment might work on is still unclear. Many of the early work is being done on melanoma, which is known to be more susceptible than many other tumors to immune system attack. It is hoped that future drugs will be able to treat lung and colorectal cancers, which have not been considered susceptible to immune attack.