It works where nothing worked before.
— Gordon Freeman, Ph.D., Dana-Farber Cancer Institute
The way we treat cancer is about to forever change. This revolution—and it is precisely that—was sparked not by the invention of a new drug, but by the evolution of an entirely new way of thinking about, and managing cancer patients. Going forward, doctors will not use pharmaceuticals to attack tumors—not directly—rather, the oncologist will treat the patient's immune system with a drug, thereby enabling it to track down and destroy the cancer.
This new branch of medicine is called immuno-oncology (IO), and to date the results from using this approach to treat cancer are without precedent.
In brief, immuno-oncology is based on the idea that, just like with any bacterial or viral infection, the human immune system is capable of recognizing, attacking, and killing tumor cells. This realization is not exactly new; what is new is that the immune system's potential for ridding the body of cancer is now being deliberately employed.
A bit of history: In the early 1900s a renowned surgeon from New York City named William Coley read about the case of a cancer patient who came down with a near-fatal, postoperative infection. That event was routine enough, but what made the case provocative was that the patient not only survived the infection, but that shortly thereafter all his remaining inoperable tumors disappeared. Coley was particularly struck by this history because he had recently operated on a patient with a very similar cancer—a patient that came though surgery with flying colors without ensuing infection, only to later die of the residual cancer that the surgery failed to remove.
After seeking out and finding a number of cases where tumors spontaneously regressed after the patient experienced a bout of infection, Dr. Coley explored and expanded on these findings and went on to develop a related cancer treatment, a bacterial preparation later dubbed "Coley's Toxins."
Unfortunately, the Toxins were only marginally effective. No one had any idea how they actually worked—if they worked at all—and after the introduction of radiotherapy, Coley's Toxins eventually fell out of favor.
Fast-forward to the early 1980s, when a researcher—another surgeon, named Steve Rosenberg (Chapter 13)—was heralded for treating cancer with a drug called IL-2, a drug that is natural to the human body and is a critical component of the immune system. Using massive amounts of this substance, Dr. Rosenberg was able to cure a number of patients with a variety of tumor types. Unfortunately, however, the treatment was highly toxic and, like Coley's Toxins, only effective in a limited number of patients. And again, the precise way the drug worked was largely unknown.
For years thereafter, the field of IO languished.
Then came “ipi.”
In 2011, a drug called ipilimumab (“ipi” for short) became the first IO agent approved by the U.S. Federal Drug Administration (FDA), thereby setting off the current IO revolution. In the pivotal clinical trial that led to ipi's approval, patients with advanced melanoma—patients with only months, if not weeks, to live—were surviving for years after being treated. In describing some of these patients, oncologists are now even using the word “cured.”
In 2014, two more IO drugs were approved: nivolumab and pembrolizumab. One of the patients to receive the latter drug—a patient that otherwise would almost certainly have already died of metastatic melanoma without this treatment—is former President Jimmy Carter. As of this writing, Carter is alive, well, and tumor-free.
This is not hyperbole. This is real.
Unlike previous attempts at IO, scientists know exactly what these two drugs are doing and, in general, that knowledge has been put to work discovering other agents and approaches that enhance the patient's immune system.
This is just the beginning. IO is here. Many hundreds of patients have already had their lives extended using this new therapeutic approach. Very soon, that number will be in the tens of thousands.