Updated overall survival (OS) results for BRIM-3, a phase III randomized, open-label, multicenter trial comparing BRAF inhibitor vemurafenib (vem) with dacarbazine (DTIC) in previously untreated patients with <i>BRAF<sup>V600E</sup></i>-mutated melanoma.
Bibliographic record
Abstract
8502^ Background: We previously reported results of the planned OS interim analysis for BRIM-3 (50% of the planned 196 deaths required for final analysis) at which time the independent Data Safety Monitoring Board recommended release of results due to compelling efficacy (hazard ratio [HR] for death, 0.37 [95% CI 0.26–0.55]); p<0.0001 and PFS HR 0.26 [95% CI 0.20–0.33]; p<0.0001) and that DTIC-treated patients be permitted to cross over to receive vem. Median follow-up for vem patients was 3.75 months, and longer follow-up would estimate median OS more reliably. Updated OS with median 6.2 months follow-up and 199 total deaths showed HR for death 0.44 (95% CI 0.33–0.59) favoring vem and median OS for vem not reached. We report here the results of an updated OS analysis performed in Nov 2011 with ~10 months median follow-up on vem. Methods: 675 patients with previously untreated, unresectable Stage IIIC or IV melanoma that tested positive for BRAFV600E mutation by the cobas 4800 BRAF V600 Mutation Test were randomized (1:1) from Jan to Dec 2010 to vem (960 mg po bid) or DTIC (1000 mg/m2 IV q3w). Co-primary endpoints were OS and PFS. OS data for DTIC patients who crossed over to vem were censored at the time of crossover. Results: Median lengths of follow-up on vem and DTIC were 10.5 months (range 0.4–18.1) and 8.4 months (range <0.1–18.3), respectively. There were 334 deaths. Median OS rates with vem and DTIC were 13.2 months (95% CI 12.0–15.0) and 9.6 months (95% CI 7.9–11.8), respectively. 12-month OS rates were 55% for vem and 43% for DTIC. HR for death was 0.62 (95% CI 0.49–0.77) in favor of vem. 81 DTIC patients crossed over to vem. 44 (13%) vem and 65 (19%) DTIC patients received ipilimumab post-progression. Conclusions: With longer follow-up, vem treatment continues to be associated with improved OS in the BRIM-3 study. An updated analysis, with estimated median follow-up of ~13 months and including response data, will be conducted in Apr 2012 and presented at the meeting.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.009 | 0.007 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.003 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".