Overall survival (OS) with first-line atezolizumab (A) or placebo (P) in combination with vemurafenib (V) and cobimetinib (C) in <i>BRAF</i><sup>V600</sup> mutation-positive advanced melanoma: Second interim OS analysis of the phase 3 IMspire150 study.
Bibliographic record
Abstract
9547 Background: Primary analysis of the phase 3 IMspire150 study (NCT02908672) demonstrated improved investigator-assessed progression-free survival (PFS) with first-line A + V + C vs P + V + C in patients (pts) with BRAFV600 mutation–positive advanced melanoma (hazard ratio [HR] 0.78; 95% CI, 0.63-0.97; P= 0.025). With median follow-up of 18.9 months at primary analysis, OS data were immature; interim analysis of OS at the time of the primary analysis demonstrated a trend in favor of A + V + C over P + V + C (estimated 2-year OS rate, 60.4% vs 53.1%) (Gutzmer et al. Lancet 2020;395:1835-1844). Herein, we present results from the second interim OS analysis of the IMspire150 study. Methods: IMspire150 enrolled previously untreated pts with stage IV or unresectable stage IIIc BRAFV600 mutation-positive melanoma (n = 514). Pts were randomized 1:1 to receive 28-day cycles of A + V + C (n = 256) or P + V + C (n = 258). Pts received V + C in cycle 1; A or P was added on days 1 and 15 from cycle 2 onwards. The second interim OS analysis was planned after ̃270 OS events were recorded, and was projected to have a minimally detectable difference of HR of 0.74 with a P value boundary of 0.0140. OS was estimated using the Kaplan-Meier method. Results: At data cutoff (Sept 8, 2021), 273 OS events had occurred. Median follow-up was 29.1 months (range, 1-54) for A + V + C and 22.8 months (range, 0-54) for P + V + C. A continued trend toward OS benefit in favor of A + V + C over P + V + C was observed with median OS of 39.0 vs 25.8 months, but the difference did not reach statistical significance (HR, 0.84; 95% CI, 0.66-1.06; P= 0.1432). A delayed treatment effect was observed, with landmark OS rates for A + V + C vs P + V + C of 76.1% vs 76.5% at 12 months and 61.5% vs 53.3% at 24 months. With additional follow-up, A + V + C continued to show PFS benefit over P + V + C (HR, 0.79; 95% CI, 0.64-0.97; P= 0.0224); overall response rates (66.7% vs 65.0%) and median duration of response (21.0 vs 12.6 months) remained consistent with those reported at primary analysis. No new safety signals were observed with additional follow-up. Conclusions: With further follow-up, A + V + C demonstrated a consistent, but not statistically significant, improvement in OS and continued benefit in duration of response versus P + V + C in previously untreated pts with BRAFV600 mutation–positive advanced melanoma. Clinical trial information: NCT02908672.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".