LBA3 Durvalumab (D) ± tremelimumab (T) + chemotherapy (CT) in first-line (1L) metastatic NSCLC (mNSCLC): 5-year (y) overall survival (OS) update from the POSEIDON study
Bibliographic record
Abstract
In the phase 3 POSEIDON study, 1L T+D+CT demonstrated statistically significant improvements in both progression-free survival (PFS) and OS (HR 0.77; 95% CI 0.65‒0.92; p=0.0030; median follow-up [FU] 34.9 mo in censored patients [pts] across all three arms) vs CT alone in pts with EGFR/ALK wild-type mNSCLC, leading to approvals for this regimen. D+CT significantly improved PFS vs CT, with a trend for OS improvement that did not reach statistical significance (HR 0.86; 95% CI 0.72‒1.02; p=0.0758). Here we report long-term OS results after median FU of >5 y. Pts (n=1013) were randomised 1:1:1 to 1L treatment with: D (until progression) ± limited-course T (up to 5 doses) + platinum-based CT (up to 4 cycles); or CT (up to 6 cycles). Stratification factors were tumour cell (TC) PD-L1 expression (TC ≥50% vs <50%; VENTANA PD-L1 [SP263] assay), disease stage (IVA vs IVB) and histology (squamous vs NSQ). Long-term FU analysis of OS was prespecified. Serious AEs were collected during long-term FU. T+D+CT showed sustained OS benefit vs CT (HR 0.76; 95% CI 0.64–0.89) at an updated data cutoff of 24 Aug 2023 (median FU 63.4 mo in censored pts), with 5-y OS rates of 15.7% vs 6.8% (Table). OS improvement with D+CT vs CT remained lower in magnitude (HR 0.84; 95% CI 0.72–1.00; 5-y OS 13.0%). Updated results suggested that OS benefit with T+D+CT vs CT continued to be more pronounced in pts with NSQ vs squamous histology (data will be presented). Consistent with earlier analyses, OS benefit was maintained with T+D+CT (but not D+CT) vs CT in pts with PD-L1 TC <1%. OS by STK11/KEAP1/KRAS mutation status will be presented. No new safety signals were identified.Table: LBA3T+D+CTD+CTCTITT, n mOS (95% CI), mo HR vs CT (95% CI)* 5-y OS (95% CI), %338 14.0 (11.7–16.1) 0.76 (0.64–0.89) 15.7 (12.0–19.9)338 13.3 (11.4–14.7) 0.84 (0.72–1.00) 13.0 (9.6–16.9)337 11.6 (10.5–13.1) – 6.8 (4.4–10.0)NSQ, n mOS (95% CI), mo HR vs CT (95% CI)† 5-y OS (95% CI), %214 17.2 (14.9–21.8) 0.69 (0.56–0.85) 20.5 (15.3–26.2)209 14.8 (11.8–18.3) 0.81 (0.66–1.00) 16.4 (11.6–21.8)214 13.0 (10.6–15.1) – 9.1 (5.6–13.6)PD-L1 TC <1%, n mOS (95% CI), mo HR vs CT (95% CI)† 5-y OS (95% CI), %125 12.7 (9.9–15.5) 0.81 (0.62–1.05) 6.1 (2.6–11.8)113 10.9 (8.1–13.5) 0.98 (0.75–1.27) 6.5 (2.9–12.2)130 11.0 (8.7–12.7) – 4.0 (1.5–8.6)*Stratified/†unstratified analysis. mOS, median OS; NSQ, non-squamous. Open table in a new tab *Stratified/†unstratified analysis. mOS, median OS; NSQ, non-squamous. Updated analyses from POSEIDON after median FU of >5 y showed durable long-term OS benefit with the approved regimen of T+D+CT (vs CT alone). These results support its use as a 1L treatment option for pts with mNSCLC, including harder-to-treat subgroups such as those with PD-L1 TC <1%.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".