Real-world comparative effectiveness and safety of pembrolizumab vs chemotherapy for previously untreated PD-L1≥50% metastatic non-small cell lung cancer.
Bibliographic record
Abstract
538 Background: In the randomized KEYNOTE-024 trial, pembrolizumab demonstrated robust efficacy in patients with PD-L1≥50% metastatic non-small cell lung cancer (mNSCLC) with median overall survival of (OS) of 26.3 months and 13.4 months in the pembrolizumab and chemotherapy groups, respectively (hazard ratio (HR)=0.62). However, it is unclear how well this efficacy translates to effectiveness in routine practice. Thus, we sought to assess the real-world effectiveness and safety of pembrolizumab for patients with previously untreated PD-L1≥50% mNSCLC compared to platinum-based chemotherapy. Methods: This was a population-based, retrospective cohort study of mNSCLC patients receiving first-line platinum-based chemotherapy (historical controls) from April 1, 2013, to January 17, 2018, or first-line pembrolizumab (cases) from January 17, 2018, to March 31, 2021, in Ontario, Canada. Baseline characteristics and outcomes were ascertained from linked administrative databases. The primary outcome was OS, assessed using Kaplan-Meier and Cox proportional hazards regression methods. Secondary safety outcomes included hospitalization, emergency department visits, specialist visits, and adverse events. To adjust for baseline differences, propensity-score matching was used to match the case and control cohorts (1:1). As a sensitivity analysis, we analyzed OS by histology subgroups (squamous versus non-squamous). Results: A total of 2,284 matched patients were included in our propensity score-matched cohort. The median OS in the pembrolizumab group (13.0 months, 95% confidence interval (CI): 11.8-14.6) was significantly longer than the chemotherapy group (9.2 months, 95% CI: 8.0-10.0), with a HR of 0.81 (95% CI: 0.71-0.92). Though pembrolizumab was also associated with improved OS in both patients with squamous (HR=0.77) and non-squamous histology (HR=0.81), pembrolizumab patients reported significantly more adverse events, specialist visits, and higher 1-year cumulative incidence of direct hospitalizations (11.5% vs 6.8%, p=0.0002). Conclusions: The results of this study confirm the survival benefit of pembrolizumab monotherapy for previously untreated mNSCLC patients with PD-L1≥50% in routine practice, though with increased toxicity and diminished benefit in the real world.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 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 | 0.000 |
| 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".