Antibody–drug conjugates versus docetaxel for previously treated advanced non-small-cell lung cancer: a systematic review and meta-analysis of randomized controlled trials
Bibliographic record
Abstract
Background: Docetaxel, following progression on immunotherapy and platinum-based chemotherapy, remains the standard of care for advanced non-small-cell lung cancer (NSCLC) but offers limited promise. Antibody–drug conjugates (ADCs) may improve outcomes in this population. Objectives: Data from the literature, mainly randomized controlled trials (RCTs), have shown discrepancies. This report evaluates the efficacy and safety of ADCs versus docetaxel in previously treated advanced NSCLC. Design: The systematic review and meta-analysis was conducted focusing on phase II/III RCTs to synthesize available evidence regarding efficacy outcomes and safety of ADCs compared to docetaxel. Data resources and methods: Databases (PubMed (MEDLINE), EMBASE, and Cochrane Library), clinical trial registries, and proceedings of global oncology conferences from January 2015 to November 2024 were screened comparing ADC versus docetaxel. Two researchers independently completed data retrieval and screening work using Covidence. The Cochrane Risk of Bias Tool (RoB 2.0) was used to assess the methodological quality of the included RCTs. The primary outcomes include progression-free survival (PFS) and overall survival (OS), while the secondary outcomes include objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). The pooled hazard ratios (HRs) and odds ratios (ORs) were meta-analyzed using the appropriate generic variance and Mantel-Haenszel methods. Random-effect models were used to compute pooled estimates. Results: Of the 212 records screened, three RCTs involving 1597 patients were included. ADCs did not significantly improve PFS (pooled HR: 0.91, 95% CI: 0.73–1.13). For OS, the pooled HR was 0.88 (95% CI: 0.78–1.00, p = 0.06), reflecting a borderline significant trend favoring ADCs, with negligible heterogeneity ( I 2 = 0%). Furthermore, subgroup analysis demonstrated a significant OS benefit in the nonsquamous cohort (HR: 0.85, 95% CI: 0.74–0.98, p = 0.03). In addition, no difference was observed in ORR (OR: 1.16, 95% CI: 0.54–2.51) and DCR (OR: 1.39, 95% CI: 0.75–2.57). Grade ⩾ 3 treatment-related AEs were significantly lower (pooled OR: 0.49, 95% CI: 0.26–0.90, p = 0.02) with ADCs, despite high heterogeneity ( I 2 = 87%). Conclusion: Overall, there was no difference between the docetaxel and the ADC treatment arms; however, our findings report a significant survival benefit in the subgroup of patients with nonsquamous NSCLC pathology treated with ADCs compared to docetaxel with a manageable safety profile. Further research is needed to address heterogeneity, refine patient selection, and obtain more mature survival data with predictive biomarkers.
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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 | 0.019 | 0.039 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.023 | 0.038 |
| Bibliometrics | 0.007 | 0.007 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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 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".