Clinical and molecular characteristics of early progressors (EPs) and long-term progression-free survivors (LTPs) from the phase 3 ADRIATIC trial of consolidation durvalumab (D) vs placebo (P) after concurrent chemoradiotherapy (cCRT) in limited-stage small-cell lung cancer (LS-SCLC).
Bibliographic record
Abstract
8014 Background: At the first planned interim analysis of ADRIATIC, consolidation D significantly improved the dual primary endpoints of overall and progression-free survival (PFS) vs P in patients (pts) with LS-SCLC and no progression after cCRT. We assess clinical characteristics, patterns of progression, and associated molecular biomarkers in EPs (pts with PFS <6 mos) and LTPs (PFS or censored after >12 mos) in the D and P arms. Methods: Pts with stage I–III LS-SCLC, WHO performance status (PS) 0/1, and no progression after cCRT were randomized to D (n=264), D + tremelimumab (n=200; arm still blinded), or P (n=266) for up to 24 months. Pre-cCRT tumor samples were collected at screening and immune-related biomarkers (CD8, MHC I, PD-L1, T-cell inflamed signature [TIS], CD8A , and STING pathway) were assessed by immunohistochemistry or RNA sequencing for their role in response to immunotherapy (IO). Results: At data cutoff (15 Jan 2024), 83 (31.4%) and 113 (42.8%) pts in the D arm and 97 (36.5%) and 100 (37.6%) in the P arm were EPs and LTPs, respectively. For EPs and LTPs, respectively: 67.5% and 61.1% in the D arm and 74.2% and 72.0% in the P arm were male; 44.6% and 54.9% in the D arm and 51.5% and 48.0% in the P arm had WHO PS 0; and 90.4% and 89.4% in the D arm and 91.8% and 89.0% in the P arm were current/former smokers. Among EPs, 47.0% vs 45.4% had extrathoracic (ET) only progression, 43.4% vs 43.3% had intrathoracic (IT) only progression, and 6.0% vs 1.0% died without progression in the D vs P arms, respectively. Among LTPs, 16.8% and 25.0% of pts in the D and P arms had progression events, which were mostly IT (D: 14.2%; P: 16.0%). Similar rates of PD-L1+ tumors were observed in EPs and LTPs in both arms (Table). Trends for higher TIS and STING pathway expression were seen in LTPs vs EPs in the D arm but not the P arm. CD8 density, and CD8A and MHC I expressions were lower in EPs vs LTPs in both arms, regardless of D vs P (Table). Conclusions: Exploratory analyses suggest similar rates of IT and ET progression with D and P in EPs, but mostly IT progression in LTPs. Compared with EPs, LTPs were generally characterized by a pre-cCRT tumor microenvironment more conducive to fostering an IO response, with higher antigen presentation and cytotoxic marker expression potentially enhancing D’s mechanism of action. Clinical trial information: NCT03703297 . D, EPs P, EPs D, LTPs P, LTPs PD-L1 TC or IC ≥1%, n (%) 25 (52.1) 32 (55.2) 40 (56.3) 42 (61.8) MHC I n, median TC score* (%) 42, 65.0 46, 75.0 66, 77.5 56, 80.0 CD8 density n, median cells/mm 2 39, 46.7 43, 50.7 57, 94.2 53, 78.7 RNASeq BEP, n 17 27 29 24 CD8A expression † 1.1 1.1 1.3 1.7 TIS value † 2.3 3.1 3.2 3.4 STING signature value † 0.28 1.4 0.90 1.4 *% MHC I-positive TCs in the total tumor area. † Median. BEP, biomarker-evaluable population; TC, tumor cell; IC, immune cell.
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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 | 0.005 | 0.006 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| 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".