Pembrolizumab (Pem) for advanced non-small cell lung cancer (aNSCLC): Efficacy and safety in everyday clinical practice.
Bibliographic record
Abstract
e20506 Background: In clinical trials, Pem improves overall survival (OS) compared to chemotherapy in a subset of patients (pts) with aNSCLC. Immune related adverse events (irAE) have correlated with improved OS in some studies. We explored efficacy and safety of Pem in a provincial population. Methods: aNSCLC pts treated with Pem between 06/2015 and 08/2018 at BC Cancer were retrospectively identified. Kaplan-Meier curves of OS from initiation of Pem were plotted and multivariable analysis (MVA) was performed with Cox proportional hazard regression models. 3, 6, and 9 month landmark Kaplan-Meier analysis was performed and log-rank tests used to determine the association of irAE subtypes with OS. Multivariable logistic regression models for irAE within 3 months of Pem initiation were also fit. Results: Characteristics of the 190 pt cohort: median age 70y (41-91), ECOG PS 2/3 at start of Pem: 34.2%, squamous histology: 22.1%, EGFR mutation: 3.7%, brain (13.7%) or liver (8.9%) metastases, PD-L1 expression ≥ 50%: 92.6%, treatment line: 1st/ ≥2nd: 74.2%/25.8%. Median cycles delivered 7 (range 1-35). With median survival follow-up of 6.1 months (range 0.03-39.8 months) and 43% pts decreased, median OS of Pem in the 1st line and ≥2nd line settings were 24.3 months (95% CI, 9.7-not reached, NR) and 13.4 months (95% CI, 8.1-NR), respectively. Pts with ECOG PS 2/3 had lower OS vs. ECOG PS 0/1 (5.8 months vs. 16.7 months, log-rank p < 0.0001). On MVA, only ECOG PS (p < 0.001) was associated with OS. 66 pts (34.7% of cohort) experienced 89 irAE; most common irAE: dermatitis (20pts), hypothyroidism (13pts), and pneumonitis (10pts). 8.4% of cohort developed grade 3 or 4 irAE; no grade 5 irAE. The odds of a grade ≥ 3 irAE within 3 months was 6.3 fold higher if ECOG 2/3 vs. 0/1 (p = 0.05). A weak association between pneumonitis and decreased OS at 9 month landmark (p = 0.09) was seen; otherwise no association with irAE subtypes at 3, 6, and 9 month landmarks was observed. Conclusions: In the whole cohort, clinical efficacy and toxicity of Pem was consistent with registration trials. Pts with ECOG PS 2/3 had a significantly lower OS and higher odds of developing grade ≥ 3 irAE than those with good ECOG PS 0/1.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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) | 0.002 | 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".