Pembrolizumab plus FLOT vs FLOT as neoadjuvant and adjuvant therapy in locally advanced gastric and gastroesophageal junction cancer: Interim analysis of the phase 3 KEYNOTE-585 study.
Bibliographic record
Abstract
247 Background: The phase 3 KEYNOTE-585 study (NCT03221426) evaluated neoadjuvant/adjuvant pembrolizumab (pembro) or placebo (pbo) + chemotherapy (chemo) followed by adjuvant pembro vs pbo in locally advanced, resectable gastric or gastroesophageal junction (G/GEJ) cancer. A separate cohort evaluated pembro + FLOT (FLOT cohort). We report results from safety and efficacy analyses of the FLOT cohort at third interim analysis. Methods: In the FLOT cohort, patients (pts) with untreated, locally advanced, resectable G/GEJ cancer were randomized 1:1 to neoadjuvant pembro 200 mg IV Q3W (pembro gp) or pbo (pbo gp) Q3W for 3 cycles + FLOT (docetaxel, oxaliplatin, leucovorin, and 5-FU) Q2W for 4 cycles. After surgery, pts received adjuvant pembro or pbo Q3W for 3 cycles + FLOT Q2W for 4 cycles, then adjuvant pembro or pbo Q3W for 11 cycles. Endpoints evaluated included safety, pathCR rate (BICR), EFS (RECIST 1.1, by investigator), and OS in the ITT. Data cut-off at third interim analysis was 09 Feb 2023. Results: A total of 203 pts were randomized (100 pembro + FLOT; 103 pbo + FLOT). Among these, 12 (6%) pts had cT1-T2, 161 (79%) had cT3, and 9 (4%) had cT4. 140 (69%) had N+ disease, and 79 (39%) had GEJ adenocarcinoma at baseline. Median follow-up was 31.6 months (mo) and 31.1 mo, respectively, at IA3. A total of 94 of 99 (95%) pts completed the neoadjuvant phase, 87 of 99 (87%) completed the surgery phase, and 45 of 77 (58%) completed adjuvant treatment. The R0-resection rate was 79% vs 80% in the pembro gp vs pbo gp, respectively. The pathCR rate was 17.0% (95% CI, 10.2-25.8) in the pembro gp and 6.8% (95% CI, 2.8-13.5) in the pbo gp, estimated difference (10.2% [95% CI, 1.3-19.7]). Median EFS was not reached (95% CI, 28.2-NR) in the pembro gp and 30.9 mo (22.8-NR) in the pbo gp (HR 0.79; 95% CI, 0.52-1.22). The 24-mo EFS rates were 66% and 57%, respectively. Median OS was not reached in either group (HR 1.04; 95% CI, 0.66-1.66). The 24-mo OS rates were 72% and 73%, respectively. Grade ≥ 3 drug-related AE rates in all phases combined were 76% and 63% in the pembro vs pbo gp, with serious drug-related AEs in 42% vs 20%, and surgery-related AEs in 20% vs 13%, respectively. A total of 3 (3%) vs 1 (1%) pt in the pembro vs pbo gp died due to a drug-related AE. Conclusions: Neoadjuvant/adjuvant pembro + FLOT was feasible with no new safety concerns. PathCR and EFS favored pembro + FLOT vs pbo + FLOT in pts with untreated, locally advanced resectable G/GEJ cancer. Clinical trial information: NCT03221426 .
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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 | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 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".