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Published on: September 8, 2021
Dabrafenib plus trametinib in unselected advanced BRAF V600-mut melanoma: a non-interventional, multicenter,
Erika Richtig1, Van A Nguyen2, Peter Koelblinger3
1Department of Dermatology, Medical University of Graz, Graz.
Objective:
The efficacy of combined BRAF and MEK inhibition for BRAF V600-mutant melanoma in a broad patient population, including subgroups excluded from phase 3 trials, remains unanswered. This noninterventional study (DATUM-NIS) assessed the real-world efficacy, safety and tolerability of dabrafenib plus trametinib in Austrian patients with unresectable/metastatic melanoma.
Methods:
This multicenter, open-label, non-interventional, post-approval, observational study investigated the effectiveness of dabrafenib plus trametinib prescribed in day-to-day clinical practice to patients ( N = 79) with BRAF V600-mutant unresectable/metastatic melanoma with M1c disease (American Joint Committee on Cancer staging manual version 7), ECOG > 1, and elevated serum lactate dehydrogenase (LDH). The primary endpoint was 6-, 12- and 18-month progression-free survival (PFS) rates. Secondary endpoints were median PFS, disease control rate and overall survival (OS).
Results:
The 6-, 12- and 18-month PFS rates were 76%, 30.6% and 16.2%, respectively. Subgroup analysis showed a significant PFS benefit in the absence of lung metastasis. The median PFS and OS were 9.1 (95% CI, 7.1-10.3) months and 17.9 (95% CI, 12.7-27.8) months, respectively. The 12- and 24-month OS rates were 62.7% and 26.8%, respectively. Subgroup analyses showed significant OS benefits in the absence of bone or lung metastasis and the presence of other metastases (excluding bone, lung, brain, liver and lymph nodes). Furthermore, S100 and Eastern Cooperative Oncology Group performance status (ECOG PS) showed a significant impact on survival. No new safety signals were observed.
Conclusion:
Despite an unselected population of melanoma patients with higher M1c disease, ECOG PS > 1 and elevated LDH, this real-world study demonstrated comparable efficacy and safety with the pivotal phase 3 clinical trials for dabrafenib-trametinib.
Insights
This study shows that dabrafenib plus trametinib is effective and safe for BRAF V600-mutant melanoma patients in real-world settings. The combination therapy demonstrated comparable outcomes to clinical trials, even in a broader patient population.
Area of Science:
- Oncology
- Dermatology
- Pharmacology
Background:
- The efficacy of combined BRAF and MEK inhibitors in a broad population of patients with BRAF V600-mutant melanoma, including those excluded from pivotal trials, requires further investigation.
- Real-world data is crucial for understanding treatment outcomes in diverse patient groups.
Purpose of the Study:
- To assess the real-world efficacy, safety, and tolerability of dabrafenib plus trametinib in Austrian patients with unresectable or metastatic melanoma.
- To evaluate outcomes in a patient population with characteristics often excluded from phase 3 trials, such as poorer performance status and elevated LDH.
Main Methods:
- A multicenter, open-label, non-interventional, post-approval, observational study (DATUM-NIS) was conducted.
- The study included 79 patients with BRAF V600-mutant unresectable/metastatic melanoma, M1c disease, ECOG performance status >1, and elevated LDH.
- Primary endpoints included 6-, 12-, and 18-month progression-free survival (PFS) rates; secondary endpoints included median PFS, disease control rate, and overall survival (OS).
Main Results:
- The 6-, 12-, and 18-month PFS rates were 76%, 30.6%, and 16.2%, respectively.
- Median PFS was 9.1 months and median OS was 17.9 months, with 12- and 24-month OS rates of 62.7% and 26.8%.
- Subgroup analyses revealed significant PFS benefits in the absence of lung metastasis and significant OS benefits in the absence of bone or lung metastasis. S100 and ECOG PS significantly impacted survival. No new safety signals were identified.
Conclusions:
- Dabrafenib plus trametinib demonstrated comparable efficacy and safety to pivotal phase 3 trials in an unselected real-world population of melanoma patients.
- The treatment showed effectiveness even in patients with advanced disease (M1c), higher ECOG performance status, and elevated LDH.
- This study supports the use of dabrafenib plus trametinib in routine clinical practice for BRAF V600-mutant melanoma, including challenging patient subgroups.
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