An open-label, multicenter safety study of vemurafenib (PLX4032, RO5185426) in patients with metastatic melanoma.
Bibliographic record
Abstract
8517 Background: Vemurafenib, a BRAF inhibitor, is associated with improved PFS and OS in patients (pts) with BRAFV600-mutant metastatic melanoma (mM). We present preliminary safety and efficacy findings from a safety study of vemurafenib in pts with unresectable stage IIIC/IV mM with BRAFV600 mutations. Methods: Pts with untreated or previously treated stage IIIC/IV BRAFV600 mutation-positive (cobas 4800 BRAF V600 Mutation Test) melanoma were enrolled. Pts received continuous oral vemurafenib 960 mg bid. Primary study endpoint was safety; efficacy (RECIST V 1.1) was a secondary endpoint. Results: Of 1,964 screened pts between Mar and Sep 2011, 914 (47%) were enrolled and 834 were evaluable for safety. Median age was 53 (21–88 years), 55% males. Median time since first mM diagnosis was 7.6 months (0–18 years). At baseline, 80% of pts had ECOG PS 0–1, 11% ECOG PS 2 (missing 9%); 27% of pts had brain metastases, and 31% had elevated LDH. Most pts had received prior systemic therapy (70%) including ipilimumab (14%), MEK and BRAF inhibitors (2%). At data cut-off (Sep 30, 2011), median treatment duration was 68 days (1–223 days) with 87% of pts still on treatment. Of 834 pts, 553 (66%) to date have reported AEs. Of 553 pts reporting AEs, 88% were related to vemurafenib, 33% Grade 3, and 1.9% Grade 4. The most common (>1%) Grade 3/4 AEs were rash (3.6%), arthralgia (3.1%), and cutaneous squamous cell carcinoma/keratoacanthoma (4.3%). Most common AEs (>10%) of any grade were arthralgia (31%), rash (29%), fatigue (22%), photosensitivity (21%), nausea (15%), and were similar irrespective of brain metastases and ECOG PS. AEs caused treatment interruption in 141 (17%) pts. Of 109 pts who discontinued treatment (13%), main reasons for withdrawal were progressive disease (60%), death (20%), AEs (6%; most commonly arthritis and abdominal pain). Tumor assessments at Week 8 of treatment were available for 302/834 (36%) pts, 61% pts achieved CR or PR, and 29% had SD. Conclusions: In a setting representative of routine clinical practice, vemurafenib is seen to be well tolerated and both safety profile and activity resemble the phase I–III data although this analysis is limited by the study duration.
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".