Patient characteristics and treatment patterns in BRAF-mutated unresectable or metastatic melanoma in the United States: A snapshot from real-world data.
Bibliographic record
Abstract
e21506 Background: BRAF mutations are found in 40-60% of patients with unresectable/metastatic melanoma (m-melanoma). Recently, several new BRAF-targeted therapies (TT) have been approved, transforming the treatment landscape for patients with BRAF-mutated (BRAFm) unresectable/m-melanoma. This analysis aimed to describe patient characteristics and treatment patterns in BRAFm unresectable/m-melanoma patients receiving treatment during November 2015-June 2021. Methods: A retrospective analysis using Flatiron Health’s database was conducted. Adult patients with unresectable/m-melanoma who had evidence of the BRAF-V600 activating mutation were included. Patients were indexed at first-line (1L) therapy initiation. Treatments of interest were classified into immuno-oncology (IO) therapies and TT. All analyses were descriptive. Results: 671 unresectable/m-melanoma patients (average age: 62.7 years, 64.1% male) were included. Among them, 64.4% of patients received IO, 34.4% received TT, and 1.2% received IO+TT. In 1L, ipilimumab+nivolumab and dabrafenib+trametinib were the most common IO (50.9%) and TT (71.9%), respectively. The median duration of 1L was 8.0 months (9.7 months in IO and 6.7 months in TT). Among IO-treated patients, 28.5% had Eastern Cooperative Oncology Group (ECOG)≥1, 23.4% had elevated lactate dehydrogenase (LDH) levels, and 4.9% had 3+ metastases identified. Among TT-treated patients, 42.9% had ECOG≥1, 27.3% had elevated LDH, and 7.8% had 3+ metastases identified. Approximately one-third of the patients (n = 204) received their 1L treatment prior to being tested for BRAF mutation; the majority of whom (90.2%) received IO. 273 patients (40.7%) advanced to a second line (2L). In 2L, 14.3% of patients received the same class of therapy as in 1L, 44.7% switched from 1L IO to 2L TT, and 35.2% switched from 1L TT to 2L IO. In 2L, ipilimumab+nivolumab (50.0%) in IO and dabrafenib+trametinib (60.7%) in TT were the most common combinations. The median duration of 2L was 5.0 months (3.7 months in IO and 6.5 months in TT). Conclusions: Despite the recent availability of TT combinations for BRAFm unresectable/m-melanoma, IO is about twice as frequently prescribed than TT in 1L. One-third of the patients received treatment before BRAFm testing results were available and most of them were prescribed IO. These findings along with elevated ECOG scores, the proportion of 3+ metastases, and elevated LDH levels seen in TT patients, suggest TT is often offered to patients with a high disease burden in the current practice settings.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".