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The Cutting Edge

A Game-changer in the Fight against Melanoma

  Pembrolizumab
  Pembrolizumab
  Pembrolizumab
 

Top: White blood cells attempt to attack a deadly melanoma cancer tumor but are blocked by a protein that rises up from the cancer cell like a shield. Second: Pembrolizumab blocks the protein and breaks down the protective shield. Bottom: After treatment with pembrolizumab, the immune system is able to resume its attack by the white blood cells, shrinking the tumors.
Graphics: Courtesy of UCLA Jonsson Comprehensive Cancer Center

The U.S. Food and Drug Administration (FDA) approved a new immunotherapy drug to treat advanced melanoma, signaling a paradigm shift in the way the deadly skin cancer is treated. UCLA led the international team of researchers testing the drug, pembrolizumab, in the largest Phase 1 study ever conducted in the history of oncology.

Pembrolizumab (Keytruda) was tested on more than 600 patients who had melanoma that had spread throughout their bodies. Because so many of the patients in the early testing showed significant long-lasting responses, the study was continued, and the FDA granted the drug “breakthrough therapy” status, allowing it to be fast-tracked for approval.

“This drug is a game-changer, a very-signifi cant advance in the treatment of melanoma,” says principal investigator Antoni Ribas, MD (FEL ’98, ’01), PhD, assistant director for clinical programs in the UCLA Human Gene Medicine Program. “For patients who have not responded to prior therapies, this drug now provides a very real chance to shrink their tumors and the hope of a lasting response to treatment.” Pembrolizumab, formerly known as MK-3475, is an antibody that targets a protein called PD-1 that is expressed by immune cells. Th e protein applies the brakes to the immune system, keeping its T cells from recognizing and attacking cancer cells and hindering therapeutic attempts to fight the disease. Pembrolizumab, in eff ect, cuts the brake lines, freeing up the immune system to attack the cancer.

“We have long believed that harnessing the power of our own immune systems would dramatically alter cancer treatment,” says Judith Gasson, PhD, senior associate dean for research at the David Geffen School of Medicine at UCLA and director of UCLA’s Jonsson Comprehensive Cancer Center. “Based upon work conducted over the past two decades, we are beginning to see the clinical benefi ts of this research in some of the most-challenging cancers.”

Generally, about one-in-10 patients responded to previous immunotherapy drugs. Some of those who responded, however, exhibited long-lived benefits, which sustained scientists’ interest in the method as an effective mechanism to fight cancer. The response and duration rates for pembrolizumab were much greater than for previous drugs, Dr. Ribas says. In the new study, 72 percent of patients responded to the drug — their tumors shrank to some degree. Overall, 34 percent of patients showed an objective response, meaning that their tumors shrank by more than 30 percent and did not re-grow.

Dr. Ribas said pembrolizumab has the potential to be used to treat other cancers that the immune system can recognize, including cancers of the lung, bladder, head and neck.

To hear melanoma survivors speak about their experiences with pembrolizumab, go to: uclahealth.org/tomstutz and uclahealth.org/kathythomas.

 

 





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