Response to osimertinib in EGF816-resistant T790M-mutated lung cancer
Bibliographic record
Abstract
A 75-year-old male with metastatic adenocarcinoma of the lung that harbored an epidermal growth factor receptor (EGFR) mutation had disease control for 16 months with EGF816, an investigational, third-generation EGFR tyrosine kinase inhibitor (TKI), in a phase I clinical trial. On disease progression, his treatment was switched to an earlier third-generation EGFR TKI, osimertinib. A rapid response occurred but was short-lived for only 10 weeks, before a rapid progression ensued. The mechanism of sequential resistance to EGF816, and subsequently, osimertinib in this male was indeterminant because of the absence of baseline genomic profiling of the tumor. Repeated molecular profiling demonstrated persistent EGFR mutations and a possibly emergent TP53 G266E mutation. This case highlighted the importance of serial biopsies for genomic analysis to understand emergent TKI resistance. As non-cross resistance may be present among the various EGFR TKI, the potential in the sequential approach in targeted therapy should be explored.
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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 | 0.000 | 0.000 |
| 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 | 0.001 | 0.001 |
| 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 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".