New class of drugs is redefining traditional cancer treatment

Posted in GUMC Stories

JUNE 11, 2015—After more than 30 years of research in the field, Michael Atkins, MD , deputy director of the Georgetown Lombardi Comprehensive Cancer Center , is confident that a cancer treatment is quickly becoming so promising that it will soon overtake use of chemotherapy and radiation, leading to a revolution in cancer care.

“That’s right. Chemotherapy and radiation will likely take a back seat in the treatment of many cancer types. ,” says Atkins, when asked to repeat his prediction. Those toxic treatments will be replaced by immunotherapy, he says — drugs that will keep a cancer patient’s immune system switched on to attack tumors.

“When a cancer is developing, it faces really only one significant enemy, and that is the body’s immune system,” said Louis Weiner, MD , Georgetown Lombardi director. Immune cells normally confront cancer cells, but the body quickly and routinely turns that assault off in order to protect against chronic inflammation. Sometimes tumors themselves turn off the immune response and, with nothing within the body to stop them, the cancer cells grow and spread.

The future of cancer care will be immune system activators tailored for smoking-related lung cancer, bladder cancer, head and neck cancer, triple negative cancer, and blood and immune system malignancies, among other tumor types, Atkins says. “These are amongst the most difficult cancers to treat today. The irony is that the worst cancers are believed to be diseases that are best suited for the novel immunotherapy approaches— there are more mutations to for the immune system to attack.

“I think there are probably some cancers that we may never be able to successfully find an immune therapy for, but I also believe immune therapy will be the dominant form of cancer treatment in five years compared with chemotherapy or radiation therapy,” Atkins explains.

And he should know. Atkins helped study the two big successes recognized to date in immunotherapy — treatment of melanoma and, recently, kidney cancer.

Building the bandwagon

At the May meeting of the American Society of Clinical Oncology (ASCO), Alan Venook, MD, the chair of ASCO’s scientific program committee and University of California, San Francisco, oncologist, recognized Atkins as a seasoned immunotherapy expert, “not someone who just jumped on the immunotherapy bandwagon, but someone who built the bandwagon.”

From Harvard Medical School, where he was a professor, and Dana Farber/Harvard Cancer Center, where he led the kidney cancer program, Atkins came to Georgetown Lombardi in 2012 to build a team that would help usher in the coming era of cancer immunotherapy.

“I came to Georgetown Lombardi because I saw a relative vacuum in melanoma care and immunotherapy research and thus an opportunity to advance these disciplines at Lombardi and throughout the capital region,” he says. “I also hoped to facilitate the integration of this novel research approach into the study of other cancers types.

“I find the prospect of collaborating with the many fine investigators at this institution very energizing,” Atkins adds.

Weiner says the time is right to focus heavily on cancer immunotherapy. “We are in the middle of a revolution,” he said, echoing the same descriptor Atkins uses. “I don’t think that is hyperbolic. Those are the kinds of observations that we’ve rarely seen in our business. What really makes it exciting is that it is not just one disease.”

Checkpoint inhibitors usher in the new era

Among his many other studies and projects, Atkins has helped pioneer the use of immunotherapy in kidney cancer. He was the senior investigator in a study published March 30, 2015, in the Journal of Clinical Oncology that found the immunotherapy drug nivolumab produced long-lasting tumor control in some patients with advanced, treatment-resistant kidney cancer.

Nivolumab is a checkpoint inhibitor. Checkpoints are molecules on immune cells that regulate the intensity of an anti-tumor response. Many tumors express molecules that, when binding to a particular checkpoint known as PD1 on immune cells, switch off the immune attack.

PD1 inhibitors, like nivolumab, unleash an immune response against tumors.  The first successes in checkpoint inhibitor immunotherapy have been in melanoma and kidney cancer “because these are very vascular cancers, so immune cells have more ready access to the tumor cells,” Atkins says. They also have a lot of mutations, so making it easier for the immune system to identify and attack the tumor cells, he says. In addition to melanoma and kidney cancer, these drugs have helped treat 15 different types of cancers including subsets of virtually every cancer, Atkins says.

Another immunotherapy, ipilimumab blocks CTLA-4, a different checkpoint molecule, and may produce synergistic antitumor effects when combined with a PD1 blocker. During the ASCO plenary session, Atkins commented that in patients with advanced melanoma, the combination of nivolumab and ipilimumab appears to produce superior antitumor efficacy compared to the agents used alone.  This combination is also undergoing exploration in other tumor types and already has shown promising results in the treatment of patients with kidney cancer.

Atkins and colleagues are currently exploring how to integrate these novel immunotherapies with standard treatments. For example, he is the overall principal investigator on a recently opened national clinical trial in which patients with melanomas containing a common driver mutation in a gene known as BRAF are randomly assigned to receive combination immunotherapy followed by inhibitor therapy at time of resistance or the alternative sequence.  The study will be conducted through the national cooperative oncology research group mechanism and will open at over 100 sites nationally. The principal objective of this study is to determine which treatment sequence leads to better long-term survival and overall quality of life in patients with BRAF mutation-driven melanoma.

Atkins has also facilitated a number of collaborations at GUMC that have led to testing of various other combination immunotherapy regimens in patients with a variety of cancers via the medical center’s Experimental Therapeutics program.

“With the proof of principle established that the reactivated immune system can attack virtually any tumor type, and with a huge repertoire of immunotherapies available to precisely restore immune function in a particular cancer, the future of immunotherapy is bright.,” Atkins says. “This is a great time in cancer research — and the rewards will soon be seen in treatment of a number of cancers.”

By Renee Twombly
GUMC Communications