Patients with BRAF V600–mutated advanced melanoma who received an immunotherapy regimen of nivolumab/ipilimumab followed by targeted therapy with dabrafenib/trametinib experienced greater overall survival (72%) compared with patients receiving the converse sequence (52%). According to the study authors, these results from the phase III DREAMseq study could be practice-changing, since many patients receive targeted therapy as their initial treatment. The study by Atkins et al (Abstract 356154), was presented during a live broadcast session of the ASCO Plenary Series on November 16, 2021.
Study Methodology
The DREAMseq Trial was designed to compare the efficacy and toxicity of the sequence of the checkpoint inhibitors nivolumab plus ipilimumab followed by a combination of the targeted drugs dabrafenib plus trametinib in patients with BRAF V600–mutated advanced melanoma who have not received prior therapy. According to the lead author of the study, Michael B. Atkins, Deputy Director of the Georgetown-Lombardi Comprehensive Cancer Center in Washington, DC, about 45% of patients have a melanoma with BRAF mutations. This type of melanoma is relatively more common in younger patients.
In this study, eligible patients were stratified by ECOG performance status of 0 or 1 and lactate dehydrogenase (LDH) level. They were randomly assigned 1:1 to receive step 1 with either nivolumab/ipilimumab (arm A) or dabrafenib/trametinib (arm B) and, if disease progression occurred, were then enrolled into step 2, receiving the alternate therapy, dabrafenib/trametinib (arm C) or nivolumab/ipilimumab (arm D).
At the beginning of the study in July 2015, 265 out of a proposed 300 patients were enrolled (133 in arm A and 132 in arm B). The median age was 61, and 63% were male. As of July 16, 2021, at a median follow-up of 27.7 months, 27 patients had switched to arm C and 46 to arm D.
The primary endpoint of the study was 2-year overall survival.
KEY POINTS
- Two-year overall survival was 72% in treatment-naive patients receiving nivolumab/ipilimumab followed by dabrafenib/trametinib compared with 52% in patients receiving the converse sequence of treatments.
- Increased overall survival was first seen after 10 months, indicating the importance of switching to targeted therapy salvage in the small percentage of patients who had rapid disease progression on initial nivolumab/ipilimumab therapy.
- Starting patients with BRAF V600–mutated advanced melanoma on immunotherapy instead of targeted therapy produces better overall survival and may be practice-changing.
Results
The researchers found that long-term overall survival was higher with the sequence of therapies that started with the immunotherapy combination (arm A) and was followed by the targeted therapy regimen (arm C) compared to the converse sequence. The 2-year survival rate for patients starting with arm A was 72% and for those starting with arm B was 52%.
Increased overall survival was first seen after 10 months, indicating the importance of switching to targeted therapy salvage in the small percentage of patients who had rapid disease progression on initial nivolumab/ipilimumab therapy. Overall grade 3+ toxicity was 60% in the patients receiving the nivolumab/ipilimumab regimen and 52% in the patients receiving the dabrafenib/trametinib regimen.
Clinical Significance
“Our findings establish definitely that even for this oncogene-driven tumor that the sequence beginning with immunotherapy rather than targeted therapy produces better overall survival for the vast majority of patients,” said Dr. Atkins, in a statement. “This is practice-changing because many patients, especially in the community oncology setting receive targeted therapy as their initial treatment.”
ASCO Expert Perspective
“The study results from DREAMseq answer one of the most important clinical questions in our care of patients with advanced melanoma,” said ASCO Expert Lynn Schuchter, MD, FASCO, in a statement. “For patients with melanoma with BRAF V600 mutation who have not received prior therapy, the results clearly show better overall survival when combination immunotherapy is selected first. In an era of remarkable advances for patients with melanoma, this study is an important addition to understanding the best approach to provide the very best care.”
The study by Atkins et al was presented during a live broadcast session of the ASCO Plenary Series on November 16, 2021. The inaugural ASCO Plenary Series session featured the latest practice-changing results in advanced melanoma and digital symptom monitoring. The session recording is now available on the ASCO website. Log-in using your ASCO.org username and password to watch.
Disclosure: For full disclosures of the study authors, visit asco.org.
