December 2024, Pharmacia, a multidisciplinary journal for pharmaceutical and allied sciences, has published the research article, “Real-world effectiveness of dabrafenib and trametinib in patients with BRAF-positive melanoma treated in routine Bulgarian clinical practice.”
This significant Real-World Evidence (RWE) study was authored by leading Bulgarian healthcare professionals, oncology experts, and Sqilline. The research offers crucial insights into the real-world outcomes and effectiveness of BRAF-targeted therapies in routine clinical practice.
Sqilline’s innovative analytics solution, Danny Platform, played the instrumental role in processing and analyzing the clinical data for this study. The platform’s ability to transform unstructured clinical data into research-ready formats has been key to enabling impactful studies and advancing oncological care.
Introduction
Malignant melanoma is a leading global cancer, accounting for approximately 1 in 5 skin cancer cases. This article evaluates the real-world effectiveness of dabrafenib and trametinib in treating patients with BRAF-positive melanoma in routine clinical practice. Analyzing data from 2018 to 2022, the retrospective study offers valuable insights into treatment outcomes and the challenges encountered in non-clinical trial settings.
Key Summary Points
Objectives
- To assess the real-world effectiveness of dabrafenib and trametinib in patients with BRAF-positive malignant melanoma in a real-world setting.
- Compare outcomes, including overall survival (OS) and progression-free survival (PFS), to pivotal clinical trials (COMBI-d and COMBI-v).
Challenges
- Limited Access to Innovative Treatments and Disease Follow-up. Routine clinical practice often lacks the resources and infrastructure to provide access to advanced therapies and disease follow-up available in clinical trials.
- Unstructured Real-World Data. Inconsistent, fragmented data requires advanced analytics tools like Danny Platform for effective processing.
- Patient Variability. Differences in demographics, adherence, and protocols between real-world practice and trials necessitate robust statistical adjustments.
Solution
Danny Platform addressed these challenges by:
- Structuring and standardizing unstructured clinical data from Electronic Health Record systems.
- Applying Iterative Proportional Fitting (IPF) for cohort alignment with clinical trial populations.
- Enabling complex, reliable analyses for meaningful comparisons with clinical trials.
Results
Patient Demographics and Cohort Characteristics
- The study analyzed real-world data (RWD) consisting of 335 patients who were treated with dabrafenib and trametinib from clinical practice between 2018 and 2022.
- About 57% (190/335) of the total patients examined were closest in terms of inclusion/exclusion criteria to the Randomized Clinical Trials (RCTs) (COMBI-d and COMBI-v).
- The median age of the cohort was 64 years. The real-world patients were a bit older but, overall, still within the expected range.
- The ECOG values are not as good as in the RCT, but both values of 0 and 1 indicate a positive overall condition.
- All the patients have a BRAF V600 mutation to be eligible for the dabrafenib + trametinib combination.
Clinical Outcomes
- Progression-Free Survival (PFS). The median PFS based on RWD is 16.1 (95% CI: NC-NC) months in comparison to 9.3 months from COMBI-d trial and 17.0 (95% CI: NC-NC) months vs. 11.4 months from COMBI-v trial.
- Overall Survival (OS). In comparison to COMBI-d, RWD outcomes were overall more favorable: OS for RWD was consistently higher than RCT over the first 24 months. Similarly, in comparison to COMBI-v, RWD outcomes were more favorable: OS was close to or higher than the RCT.
- Clinical Benefit Rates (CBR) were comparable: RWD is 84.6% (95% CI: 77.9–89.5) vs. 92% for COMBI-d and 90% for COMBI-v.
Safety and Tolerability
- Adverse event profiles were consistent with clinical trial results, with most patients experiencing manageable side effects such as fever, fatigue, and rash.
- There were no new or unexpected safety concerns observed in the real-world cohort.
Statistical Adjustments and Analysis
- Iterative proportional fitting (IPF) was applied to account for differences in patient demographics and clinical characteristics between the real-world cohort and clinical trial populations. This ensured meaningful and valid comparisons of outcomes.
Broader Implications:
- Danny Platform is a proven tool for clinical outcomes follow-up, providing a scalable and efficient way to track patient progress in real-world setting.
- The study emphasized the feasibility of replicating the success of BRAF-targeted therapies in routine practice, even in resource-constrained healthcare settings.
- Results validated the use of real-world data (RWD) to complement clinical trials, demonstrating its importance in shaping personalized treatment strategies and improving outcomes for melanoma patients.
Benefits
- Validated Treatment Integration: Reinforced the practicality of dabrafenib and trametinib in standard melanoma care.
- Informative Insights: Results can guide clinical protocols, resource allocation, and health policy decisions.
- Danny Platform’s Role: Demonstrated its capacity to process large-scale RWD, advancing oncology research and enabling impactful studies.