Safety and clinical efficacy of programmed cell death 1 antibodies (PD-1 Ab) in patients with advanced non-small cell lung cancer (NSCLC).
Bibliographic record
Abstract
260 Background: In advanced NSCLC, clinical trials have shown significant benefits to pembrolizumab (P) and nivolumab (N). At BC Cancer, clinicians utilize protocol based algorithms to manage immune related adverse events (irAE). The incidence of irAE and efficacy of PD-1 Ab in everyday practice might differ from clinical trials. Methods: Advanced NSCLC patients (pts) treated with N or P between 11/2015 to 10/2017 at BC Cancer were identified. Demographic, tumor, treatment details, and frequency and grade (Gr, CTCAE v4.0) of irAE, were abstracted. Kaplan-Meier curves of median overall survival (OS) from initiation of PD-1 Ab were generated. Multivariable analysis (MVA) with 6-week landmark analysis was performed with Cox proportional hazard regression models. Results: Characteristics of cohort (230 N- and 41 P- treated): median age 64y (range 39-82), non-squamous histology 75%, ECOG PS > 1 at start of PD-1 Ab 31%, brain metastases (mets) 13%, liver mets 12%, and median Charlson Comorbidity Index (CCI) score 6. One hundred sixteen pts experienced 169 separate irAE: Gr1(74), Gr2 (68), Gr3(13), Gr4(10), Gr 5(4). Pneumonitis (14.6% vs. 4.8%, p = 0.041) and arthralgias (12.2% vs. 3.5%, p = 0.044) were more common in P than N. Steroids were administered to 25.2% of N pts and 19.5% of P pts (p = 0.557). Median follow-up from initiation of PD-1 Ab was 8.1months (range 0.1-33.9); median OS (95% CI) for N was 9.2 months (7.75-12.4) and for P was 13.5 months (10.6-not reached). 6-week landmark MVA for whole cohort revealed that male sex (p = 0.051), CCI≥3 (p < 0.001), ECOG PS > 1 (p < 0.001), liver mets (p = 0.017) and development of irAE > Gr2 versus no irAE (p = 0.036) were associated with decreased OS. Age, smoking status, histology, brain mets, EGFR status, irAE Gr 1/2 versus no irAE, and type of PD-1 Ab were not significant. Conclusions: Severe irAE were rare; pneumonitis and arthralgias were more common in P- than N- treated patients. The association with CCI, ECOG PS, and liver mets with decreased OS are consistent with literature. Association of severe irAE with shorter OS might reflect the need for improved physician education in irAE treatment algorithms.
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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 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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 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".