Upfront immunotherapy was far superior to upfront BRAF/MEK inhibition in patients with metastatic BRAFV600-mutant melanoma, causing the phase 3 DREAMseq early to stop early.
Clinical research takes years – sometimes decades – to conduct, and often includes lengthy follow-up before researchers and clinicians definitely understand the benefit of a therapy being tested. However, a clinical trial examining a treatment regimen for patients with melanoma was recently stopped because the benefit of upfront immunotherapy was strikingly clear.
The phase 3 DREAMseq clinical trial was examining Tafinlar (dabrafenib) and Mekinist (trametinib) followed by Yervoy (ipilimumab) and Opdivo (nivolumab) or Yervoy/Opdivo (both immunotherapy drugs) followed by Tafinlar and Mekinist (BRAF/MEK inhibitors) in patients with stage 3 or 4 BRAFV600-mutant melanoma.
The trial ended early because the benefit of receiving the immunotherapy combination first was very apparent: the two-year survival rate was 72% in patients who received Yervoy/Opdivo first compared to 59% in the group that received Tafinlar/Mekinist first.
“The drug combinations tested in this trial all improve survival compared to prior standards of care, but we now know which combination should be administered first to achieve maximum benefit for the vast majority of our patients,” said Dr. Michael Atkins, the trial’s principal researcher, deputy director, professor and acting chief in the division of Hematology/Oncology at MedStar Georgetown University Hospital, in a press release.
When presenting the trial findings at the American Society of Clinical Oncology Virtual Plenary Series, Atkins also explained that 100 patients died while on the trial – 62 of them were randomized to receive the BRAF/MEK inhibitor combination first. Those who did die on the immunotherapy-first treatment plan tended to have poorer prognoses.
“The data safety monitoring committee felt that there was a clinically meaningful difference in overall survival and recommended that the study be closed to approval and patients on first-line (Tafinlar/Mekinist) given the option to switch to Arm D, (Yervoy/Opdivo) without the need for disease progression,” Atkins said in his presentation.
Looking forward, Atkins said that these findings should help to inform treatment decisions for patients with advanced BRAFV600-mutant melanoma, as well as other cancer types.
“This trial should provide clearer guidance to clinicians on when to administer particular treatments,” Atkins said. “While this trial focuses on melanoma, it could have significant implications for the treatment of other forms of cancer where immunotherapies are increasingly part of treatment regimens.”
However, more research is needed, especially for the subset of patients who do not benefit as much as others on immunotherapy.
“One conundrum in the data showed that some patients don’t do well on initial immunotherapy treatments, and for some reason switching to targeted therapies did not help,” says Atkins. “We are focusing on trying to determine why there was no benefit for this small group of patients.”
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