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The Cutting Edge

Three-drug Combination Helps Curb the Growth of Deadly Type of a Cancer

A UCLA-led research team has pinpointed a three-drug combination that could prove to be an effective new therapy for people with a specific type of advanced melanoma.

Three drug Combination Helps Curb the Growth of Deadly Type of a Cancer

Patients in this study received daily dosing with the BRAF inhibitor dabrafenib taken orally twice daily at 15 mg, the MEK inhibitor trametinib taken orally once daily at 2 mg and intravenous infusions of the anti-PD-1 antibody pembrolizumab every 3 weeks at 2 mg/kg.
Graphic: Courtesy of Dr. Antoni Ribas

 

The approach shows promise for extending the lives of people with a type of melanoma that contains a potent gene mutation, BRAF V600E. In clinical trials, it appeared not to cause the debilitating side effects that are caused by a combination of one targeted drug and an immunotherapy drug.

The researchers found that people with the melanoma survived longer without the cancer progressing or growing when they received a combination of two targeted inhibitors that block the BRAF mutation (dabrafenib and trametinib) and an immune checkpoint inhibitor drug (pembrolizumab) as the initial treatment for their disease.

“Utilizing the three drugs together sensitized the patient’s own immune system to bolster the power of immunotherapy and block the growth of two genes — BRAF and MEK — that cause cancer cells to reproduce and grow out of control,” says Dr. Antoni Ribas, MD (FEL ’98, ’01), PhD, professor of medicine and director of the UCLA Jonsson Comprehensive Cancer Center’s Tumor Immunology Program.

In the phase one trial, the scientists tested the three-drug combination for safety in 15 people with BRAF-mutated metastatic melanoma. In 11 of them, the tumors shrank and remained stable and did not grow again for 12 to 27 months. In the phase two trial, those who received the three-drug combination had progression-free survival — meaning that the disease did not worsen or progress — for an average of 16 months. Those who received trametinib, dabrafenib and a placebo lived for an average of 10.3 months without the disease progressing.

Previous studies have found that using one of the three drugs alone can dramatically shrink tumors in a small percentage of people with melanoma. A majority of people on the treatment, however, do not see any benefit or end up experiencing a relapse. Two-drug combinations also have been tested, but they, too, have had limited success. “Earlier attempts to combine a targeted agent with an immune checkpoint inhibitor as a double-combination therapy had debilitating side effects for patients, and it was just too toxic to continue testing, so we went back to the drawing board,” says Dr. Ribas, who also is director of the Parker Institute for Cancer Immunotherapy Center at UCLA. “We found that by using two targeted inhibitors, instead of just one, in combination with a checkpoint inhibitor, we could safely and effectively treat the cancer.”

— Denise Heady

“Combined BRAF and MEK Inhibition with PD-1 Blockade Immunotherapy in BRAF-mutant Melanoma,” Nature Medicine, June 6, 2019.

“Dabrafenib, Trametinib and Pembrolizumab or Placebo in BRAF-mutant Melanoma,” Nature Medicine, June 6, 2019.


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Fall 2019

Fall 2019
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IN THIS ISSUE
  • Unlocking the Unknown: The Power and Promise of Collaboration
  • Students Travel to a Remote Peruvian City to Learn about Medicine with Limited Resources
  • The Brains of Pairs of Animals Synchronize during Social Interaction
  • More HPV Vaccinations could Prevent Cancer in 1,300 Californians
  • Antibiotics before Liver Transplants Leads to Better Results
  • Immunotherapy Improves Five-year Survival Rate of People with Advanced Lung Cancer
  • Research Explains How Eyes See Continuously in Bright Light
  • Three-drug Combination Helps Curb the Growth of Deadly Type of a Cancer
  • Peptides that Mimic ‘Good Cholesterol’ Reverse Inflammatory Bowel Disease in Mice
  • Giving Where the Rubber Meets the Road
  • The Accidental Scientist
  • Answers, At Last
  • Coal Miner’s Son
  • A Day in the Life: Child Life Specialists in the Operating Room
  • Journey of a Lifetime
  • Awards & Honors
  • In Memoriam
  • Sold-out Wonder of Women Summit Celebrates Whole Health
  • UCLA Receives $10 million from The Eli and Edythe Broad Foundation to Support Stem Cell Research
  • Taste for a Cure Raises Money for Cancer Research
  • Cyclists Help Tour de Pier Surpass Fundraising Target
  • UCLA Jonsson Comprehensive Cancer Center Names New Research Suite
  • Semel Institute Introduces 2018-19 Max Gray Fellows
  • UCLA Women’s Cardiovascular Center Hosts a Community Update on Women’s Heart Health
  • Vision Specialists Establish Smotrich Family Optometric Clinician-Scientist Chair
  • UCLA Stein Eye Institute Celebrates the Bert O. Levy Chair
  • Innovations in Nutrition and Mindfulness on the Road to Health and Wellness
  • Two Young Friends Launch Toy Drive to Benefit Mattel Patients
  • Gifts
  • In Memoriam
  • Thanks to the Ants
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