New Cancer Drug Harnesses the Immune System

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A new cancer immunotherapy drug called Atezolizumab has proven to be highly effective against advanced bladder cancer, with fewer side effects than chemotherapy and other drugs, and less likelihood of tumor regrowth. The researchers presented their findings at the annual meeting of the American Society for Clinical Oncology (ASCO) in early June.

Bladder cancer is the fifth most common cancer in the U.S. according to study lead author Arjun Balar, assistant professor of medicine and co-leader of the genitourinary cancers program at the NYU Perlmutter Cancer Center. “It tends to favor men over women, and there are 15,000 to 16,000 deaths per year in the United States from it,” he tells mental_floss. By the time the disease is in the advanced stage, fewer than 15 percent of people survive longer than five years.

Atezolizumab (also known as Tecentriq), which was only just approved by the FDA in May, is what’s known as a checkpoint inhibitor, or a drug that blocks specific antibodies; in the case of metastatic bladder cancer, it blocks the protein PD-L1 from interacting with its receptor partner, PD-1. “If you use an antibody or drug that blocks that interaction, which is what the drug does, you can’t activate the [immune system’s] brakes anymore, and the immune system attacks the cancer,” Balar says.

Of 119 study participants with metastatic bladder cancer, after receiving atezolizumab, 28 of them, or 24 percent, had tumors shrink by at least 30 percent within 15 weeks, with no new detectable cancer growth. The drug also extended the average survival time from just under a year to almost 15 months.

While chemotherapy can bring a higher instance of tumor reduction—as much as 40 percent, according to Balar—"the difference with chemotherapy drugs is [tumors] shrink, but then they grow again, almost universally," he explains. "Whereas, with immune therapy drugs, they shrink and they tend to stay that way. And patients also feel better.”

Patients feel better because atezolizumab only caused mild side effects such as fatigue, itchy skin, and diarrhea. “Compared to chemotherapy, it’s extremely well tolerated, and even when you do develop a side effect, [it is] very manageable,” says Balar.

Compare that with the commonly used chemotherapy drug for bladder cancer, cisplatin, which kills tumor cells through a process that prevents them from repairing damage to their DNA and causes significant toxic side effects to nerve, kidney function, and hearing. That rules cisplatin out as a drug for the elderly population that comprises approximately half of bladder cancer patients.

Immunotherapy drugs may soon take priority over chemotherapy drugs for their unique ability to focus specifically on cancer cells. “Chemotherapy kills a lot of different good cells and bad cells,” says Balar. He points out that the immune system also has “a memory,” so that once it knows which types of cells are bad and how to kill them, it keeps that knowledge and function for the lifetime of that immune cell. “That adaptability, memory, and the specificity are what make the immune system such a powerful weapon against cancer,” he says.

Next, Balar is working on two big projects; one to combine atezolizumab with another immune drug, to see how well they work together, and a second trial that will combine another immune drug with radiation, to see if that combination works well in bladder cancer patients where the cancer is confined to the bladder.

A caveat on this study: Balar is a paid consultant to atezolizumab manufacturer Genentech, which funded the current study. On the other hand, he's also received research support from Merck, which is developing a competing immunotherapy to atezolizumab.

Balar is pleased with the extended lifespans of the patients in the trial and hopes to see that number improve over time. “What we’re seeing is that maybe the immune therapy is working in ways beyond just shrinking tumors," he says. "It’s altering the disease course for some people.”