Event-free survival (EFS) in MATTERHORN: A randomized, phase 3 study of durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel chemotherapy (FLOT) in resectable gastric/gastroesophageal junction cancer (GC/GEJC).
Bibliographic record
Abstract
LBA5 Background: FLOT is a perioperative standard of care (SoC) in resectable GC/GEJC, yet recurrence rates remain high. Immune checkpoint inhibitors are approved in combination with chemotherapy in metastatic GC/GEJC, but not in the perioperative setting. The randomized, double-blind, global, Phase 3 MATTERHORN study (NCT04592913) assesses the combination of perioperative durvalumab (D) + FLOT vs placebo (P) + FLOT in participants (pts) with locally advanced, resectable GC/GEJC. The primary endpoint is EFS. Pathologic complete response (pCR) and overall survival (OS) are key secondary endpoints. The trial previously showed a statistically significant gain in pCR for D + FLOT. Here, we report efficacy and safety from the pre-planned interim analysis 2. Methods: Pts aged ≥18 years with histologically confirmed, resectable (Stage II–IVa per American Joint Committee on Cancer 8th edition) untreated G/GEJ adenocarcinoma were randomized 1:1 to D 1500 mg or P every 4 weeks (Q4W) on Day 1 + FLOT on Days 1 and 15 for 4 cycles (2 cycles each neoadjuvant/adjuvant), followed by D 1500 mg or P on Day 1 Q4W for 10 cycles. Pts were stratified by Asia vs non-Asia, clinical lymph node status (positive vs negative) and programmed cell death ligand-1 Tumor Area Positivity score (≥1% vs <1%). Data cutoff was Dec 20, 2024. EFS (time from randomization to progression, local or distant recurrence, or death) superiority for D + FLOT vs P + FLOT was assessed in all randomized pts by a stratified log-rank test (2-sided significance level threshold: 0.0239) on data according to RECIST v1.1 per BICR and/or locally by pathology testing. Results: In total, 948 pts were randomized to receive D + FLOT (n=474) or P + FLOT (n=474); median (m) follow-up duration was 31.5 months (mo). Demographic/baseline characteristics were generally similar across treatment arms. D + FLOT demonstrated a statistically significant improvement in EFS vs P + FLOT (hazard ratio [HR] 0.71; 95% confidence interval [CI], 0.58–0.86; p<0.001), mEFS was not reached (NR) with D + FLOT vs 32.8 mo with P + FLOT. The 24-mo EFS rate was higher for D + FLOT vs P + FLOT (Table). mOS was NR for D + FLOT vs 47.2 mo for P + FLOT (HR 0.78; 95% CI, 0.62–0.97; p=0.025; 33.9% maturity) and will be formally assessed at the final analysis. Maximum Grade 3 or 4 adverse event rates were similar between treatment arms; D + FLOT did not delay surgery or initiation of adjuvant therapy vs P + FLOT. Conclusion: D + FLOT demonstrated a statistically significant improvement in EFS vs P + FLOT in pts with resectable GC/GEJC, with an encouraging OS trend. These results support D + FLOT as a potential new global SoC for resectable GC/GEJC. Clinical trial information: NCT04592913 . D + FLOT (n=474) P + FLOT (n=474) mEFS (95% CI), mo NR (40.7–NR) 32.8 (27.9–NR) EFS rate (95% CI), %12 mo24 mo 78.2 (74.1–81.7)67.4 (62.9–71.6) 74.0 (69.7–77.8)58.5 (53.8–63.0)
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.008 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".