Advertisement


Georgina V. Long, MD, PhD, on BRAF-Mutated Melanoma: Long-Term Follow-up of Adjuvant Dabrafenib Plus Trametinib vs Placebo

2024 ASCO Annual Meeting

Advertisement

Georgina V. Long, MD, PhD, of the Melanoma Institute Australia and The University of Sydney, discusses final results with up to 10 years’ follow-up data of the COMBI-AD study of patients with stage III BRAF-mutated melanoma who received adjuvant dabrafenib plus trametinib (Abstract 9500).



Transcript

Disclaimer: This video transcript has not been proofread or edited and may contain errors.
COMBI-AD trial is a randomized phase three clinical trial of adjuvant dabrafenib combined with trametinib versus placebo for resected stage three BRAF mutated melanoma. The final analysis, the long-term data and the overall survival data were presented and show a durable and sustained benefit in terms of relapse-free survival when patients received dabrafenib plus trametinib versus placebo. There was a 48% reduction in the risk of recurrence with nearly 10 years of follow-up. In fact, the median follow-up was 100 months for dabrafenib plus trametinib and 82 months for placebo, and the maximum follow-up was 125 months. So when we look at the relapse-free survival and look at the eight-year relapse-free survival landmark, we saw 50% for dabrafenib and trametinib, which was much higher than the 35% we saw for placebo. Again, we saw a sustained and durable improvement in the distant metastasis-free survival with a hazard ratio of 0.56, that's a 44% reduction in the risk of distant metastasis at first recurrence. So therefore, the two major endpoints were statistically significant with confidence intervals that did not cross one demonstrating this durable and sustained impact of adjuvant dabrafenib-trametinib. The overall survival showed a separation of the Kaplan-Meier curves with a 20% reduction in the risk of death from any cause using adjuvant dabrafenib-trametinib versus placebo. This is a hazard ratio of 0.80. However, the confidence interval just nudged over one, 1.01, and the P-value is 0.063 so this was not statistically significant. We will not see an adjuvant trial which has any separation of the Kaplan-Meier curves. So this is substantial for the modern era of melanoma treatments when we know that we can cure patients in the advanced setting to see any separation of the overall survival curves in the stage three setting. What was remarkable is if we looked at the subgroup of V600E, they seem to benefit the most in terms of overall survival. The dabrafenib-trametinib hazard ratio versus placebo was 0.75, that's a 25% risk reduction terms of death using adjuvant dabrafenib and trametinib for those with the V600E and that was 91% of the trial population. However, for V600K, which was a small subgroup, there was a reversal, the placebo arm seemed to do better than dabrafenib-trametinib, but we have to exercise caution with only 40 and 37 patients in each arm for that analysis, but it does suggest that the main benefit seems to be in patients with V600E melanoma. Interestingly, the relapse-free survival benefit with dabrafenib and trametinib was seen for both V600E, and V600K. So it was only the overall survival where we saw really the substantial benefit in the V600E. So what does this mean for the future? It means that we have a treatment that can be used for BRAF V600 mutated patients for adjuvant therapy for resected stage three. There were no irreversible toxicities with this long-term follow-up data, and we saw a sustained and durable impact on the relapse-free survival, the distant metastasis-free survival, and we did see a numerical improvement in the overall survival as well as the melanoma-specific survival, a very important endpoint as we cure more patients with melanoma.

Related Videos

Lymphoma

Joshua D. Brody, MD, on Follicular Lymphoma: New Data on Epcoritamab, Rituximab, and Lenalidomide

Joshua D. Brody, MD, of the Icahn School of Medicine at Mount Sinai, discusses results from the EPCORE NHL-2 study, which was designed to evaluate the safety and efficacy of epcoritamab-bysp plus rituximab and lenalidomide in the first-line setting for patients with follicular lymphoma and to assess epcoritamab as maintenance therapy in this population (Abstract 7014).

Breast Cancer

Reshma Jagsi, MD, and Christian F. Singer, MD, MPH, on Early-Stage Breast Cancer: Adding a Vaccine to Neoadjuvant Systemic Therapy

Reshma Jagsi, MD, DPhil, of Emory University Winship Cancer Institute, and Christian F. Singer, MD, MPH, of the Medical University of Vienna, discuss the MUC-1 vaccine tecemotide. When added to standard neoadjuvant systemic therapy for patients with early-stage breast cancer, this vaccine improved distant relapse–free and overall survival rates. Despite the exploratory nature of this observation, says Dr. Singer, this is the first long-term survival benefit of an anticancer vaccine in breast disease reported to date (Abstract 587).

Skin Cancer

Christian U. Blank, MD, PhD, on Melanoma: Potentially Practice-Changing Results From the NADINA Trial

Christian U. Blank, MD, PhD, of the Netherlands Cancer Institute, discusses findings of an investigator-initiated phase III trial showing that neoadjuvant ipilimumab plus nivolumab followed by response-driven adjuvant treatment improved event-free survival in patients with macroscopic, resectable stage III melanoma compared with adjuvant nivolumab (LBA2)

Lymphoma

Peter Riedell, MD, on DLBCL: Expert Commentary on the DEB Study

Peter Riedell, MD, of The University of Chicago, discusses phase III results on the use of tucidinostat plus R-CHOP in patients with previously untreated diffuse large B-cell lymphoma (DLBCL) with double expression of MYC and BCL2. The regimen appeared to improve event-free survival and complete response rates vs R-CHOP in the front-line setting. As this is an interim analysis, longer-term follow-up will be needed to better understand its impact, says Dr. Riedell.

Skin Cancer

Pauline Funchain, MD and Paolo A. Ascierto, MD, on Advanced Melanoma: Results From the RELATIVITY-048 Trial

Pauline Funchain, MD, of Stanford University and the Stanford Cancer Institute, and Paolo A. Ascierto, MD, of Italy’s Istituto Nazionale Tumori and IRCCS Fondazione G. Pascale, discuss efficacy and safety findings of the triplet therapy nivolumab, relatlimab-rmbw, and ipilimumab in patients with advanced melanoma (Abstract 9504).

 

Advertisement

Advertisement




Advertisement