Practice Changing Study Highlights Value of Starting Immunotherapy Before Targeted Therapies in Patients with BRAF-Mutated Melanoma

HACKENSACK, N.J., Oct. 4, 2022 /PRNewswire/ -- Michael Atkins M.D. national lead Investigator and Andrew Pecora M.D., co-investigator, senior attending members of the NCI designated Georgetown Lombardi Comprehensive Cancer Center Consortium participated with other prominent national investigators in completing the phase III DREAM seq trial that generated results that will guide the practice of care globally for patients with advanced BRAF mutated melanoma. The study was published in the September 27, 2022 issue of the Journal of Clinical Oncology.

Dr. Atkins working at the Consortium Cancer Center's Georgetown campus (in conjunction with MedStar Health) in Washington D.C and Dr. Andrew Pecora at the John Theurer Cancer Center campus, (part of Hackensack Meridian Health) in Hackensack New Jersey, worked collaboratively through the NCI designated consortium with other national investigators in this randomized trial that showed a significant survival advantage among patients with BRAF-mutated advanced melanoma who received combined (anti PD-1 and anti CTLA-4) checkpoint inhibitor therapy as the first line of therapy followed by targeted therapy with dabrafenib and trametinib on progression as compared with patients with BRAF-mutated melanoma who first received targeted therapy followed by checkpoint inhibitor therapy on progression.

"The survival advantage at two years was striking when checkpoint inhibitor therapy was sequenced before targeted therapy (72% [95% CI; 62-81%] versus 52% [CI; 42-62%] p=0.0095)," says Atkins.

"This data will guide physicians around the globe who care for patients with BRAF-mutated metastatic melanoma on the proper order of treatment so as to obtain the best survival," said Dr Pecora.

"This trial and our cancer centers participation together truly demonstrates the power of our NCI designated consortium and level of importance of the practice changing research we are doing together in Washington and New Jersey," Dr Louis Weiner Director of the Georgetown Lombardi Comprehensive Cancer Center said. "The DREAMseq trial led by Dr. Atkins is an example of how our consortium based in Washington DC and Hackensack New Jersey is conducting translational and clinical trial research together that promises to change how oncologists deliver cancer care globally".

About 99,780 people are estimated to receive a new diagnosis of melanoma in 2022 and more than 7,000 are projected to die of the disease, according to the American Cancer Society. While melanoma rates rose rapidly over the past few decades, the latest Annual Report to the Nation on the Status of Cancer noted that mortality rates are now declining — reflecting a significant increase in survival due to improved treatment options, among other factors.

"This collaboration demonstrates the impact of collaboration between John Theurer Cancer Center and Georgetown Lombardi Comprehensive Cancer Center through the NCI-designated consortium, which will change clinical practice across the globe to improve the lives of people with advanced melanoma,'' said Robert C. Garrett, chief executive officer of Hackensack Meridian Health. "It is an example of our commitment to caring for people with cancer not only within, but beyond, the walls of our hospitals.''

About half of melanoma cases carry mutations in key proteins that control cell growth, such as BRAF, which can be targeted with a combination of dabrafenib (a BRAF inhibitor) and trametinib (a MEK inhibitor). Immunotherapy boosts the power of the immune system to fight cancer. Targeted medications and immunotherapy have become standard care for people with advanced melanoma. But one of the biggest questions in oncology has been determining the best sequence of treatments.

Starting in 2015, 265 patients with metastatic melanoma were randomly assigned to one of two groups. One group started treatment with combination ipilimumab and nivolumab immunotherapy, and the second group began with the targeted therapies dabrafenib and trametinib. Ipilimumab and nivolumab, which are given intravenously, work by taking the brakes off the immune response, enabling immune cells to find and destroy cancer cells. Dabrafenib and trametinib are pills that, when given together, inhibit the function of the proteins associated with the BRAF V600E mutation, leading to direct killing of tumor cells. Patients in each group could receive the other drug combination if the first treatment failed to control their cancer.

The clinical trial was stopped after two years. Two-year overall survival was 72% among patients who received combination immunotherapy first versus 52% for those who took the two targeted therapies as initial treatment. Progression-free survival, where the cancer remains stable or improves, also tended to be better for the immunotherapy group.

The new study provides strong evidence demonstrating how best to treat patients with advanced melanoma that contains a BRAF V600E mutation: immunotherapy is the better initial approach, even for people whose tumors have a mutation that could be treated by targeted therapies.

Hackensack Meridian John Theurer Cancer Center is New Jersey's largest and most comprehensive center dedicated to the diagnosis, treatment, management, research, screenings, and preventive care as well as survivorship of patients with all types of cancers. The 14 specialized divisions covering the complete spectrum of cancer care have developed a close-knit team of medical, research, nursing, and support staff with specialized expertise that translates into more advanced, focused care for all patients. Each year, more people in the New Jersey/New York metropolitan area turn to John Theurer Cancer Center for cancer care than to any other facility in New Jersey. John Theurer Cancer Center is a part of the Georgetown Lombardi Comprehensive Cancer Center, an NCI-designated Comprehensive Cancer Center. Housed within a 775-bed not-for-profit teaching, tertiary care, and research hospital, John Theurer Cancer Center provides state-of-the-art technological advances, compassionate care, research innovations, medical expertise, and a full range of aftercare services that distinguish John Theurer Cancer Center from other facilities. For additional information, please visit www.jtcancercenter.org. 

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SOURCE Hackensack Meridian John Theurer Cancer Center