Updated molecular analyses of exons 19 and 21 of the epidermal growth factor receptor (<i>EGFR</i>) gene and codons 12 and 13 of the <i>KRAS</i> gene in non-small cell lung cancer (NSCLC) patients treated with erlotinib in National Cancer Institute of Cancer
Bibliographic record
Abstract
7571 Background: BR.21 demonstrated significant survival benefit from erlotinib for NSCLC patients (Shepherd, NEJM 2005). EGFR gene point mutations in exon 21 and deletions in exon 19 predict response to EGFR TKIs, but the predictive value of EGFR mutations (Mut) or high copy number (Amp) on survival remains unclear. Methods: The sensitivity of PCR-sequencing to detect EGFR mutations may be suboptimal. Thus, we re-analyzed all BR.21 samples with available material using a fluourescent-based PCR technique (Pan, JMD 2005;7:396) and ScorpionIM kits (DxS, Manchester, UK) as they may detect mutations in samples with only 5–10% tumor DNA. 204 samples were analyzed successfully for EGFR Mut, 206 for KRAS Mut and 159 by FISH for EGFR Amp. Results: Exon 19 deletion and/or exon 21 L858R Mut were identified in 34 patients (overall Mut rate 17%). EGFR high polysomy or true amplification was present in 61 patients (38%), and 30 patients (15%) had KRAS Mut. Overall response rates were EGFR wildtype (WT)/Mut: 7%/27%, p=0.03; KRAS WT/Mut: 10%/5%, p=0.69; No Amp/Amp: 5%/21%, p=0.02. Hazard ratios for survival benefit were EGFR WT: 0.74 (0.52–1.05, p=0.09), Mut: 0.55 (0.25–1.19, p=0.12); KRAS WT: 0.69 (0.9–0.97, p=0.03), Mut: 1.67 (0.62–4.50, p=0.31); no Amp: 0.80 (0.49–1.29, p=0.35), Amp: 0.43 0.23–0.78, p=0.004). The test for interaction was borderline for KRAS Mut (0.09) but was not significant for EGFR Mut (p=0.47) or EGFR Amp (0.12). It was significant only for non-smokers with EGFR Amp (p=0.04). In the multiple Cox regression model, including all markers, EGFR Amp was both prognostic for poorer survival (p=0.005) and predictive of a differential survival benefit from erlotinib (p=0.009). EGFR and KRAS Mut were not significant prognostic or predictive markers. Conclusion: EGFR genotype and copy number are predictive of objective response to erlotinib. In BR.21, EGFR gene copy number is the strongest molecular prognostic marker and the only significant molecular predictor of a differential survival benefit from treatment. [Table: see text]
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".