Afatinib as a novel potential treatment option for <i>NRG1</i> fusion-positive tumors.
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
110 Background: Neuregulin 1 (NRG1) is a growth factor that binds HER3/4 and activates ErbB signalling pathways. NRG1 gene fusions function as oncogenic drivers and represent a potential therapeutic target across tumour types. Afatinib, an ErbB-family blocker, is a potential treatment option for some patients with NRG1 fusion-positive ( NRG1+) tumours, as supported by preclinical evidence and clinical case reports. Of 13 patients with NRG1+ lung adenocarcinoma (ADC; n = 9), pancreatic ADC (n = 2), cholangiocarcinoma (n = 1), and ovarian cancer (n = 1) treated with afatinib, eight patients achieved a best response of partial response (PR; median duration 7.3 months, range 3–12), three patients had stable disease (SD) and two patients had progressive disease. Methods: Here, we report the clinico-pathological and molecular characteristics and current status of four additional cases of afatinib-treated NRG1+ tumours. Results: Patient 1, 66 year-old female, never-smoker with metastatic non-mucinous lung ADC. CD74-NRG1 fusion was identified, and 5 th -line afatinib initiated. PR is ongoing after 16 months. Patient 2, 43 year-old female, non-smoker with advanced invasive mucinous lung ADC. CD74-NRG1 fusion was identified and 3 rd -line afatinib initiated (PR, 18 months); treatment is ongoing following local progression. Patient 3, 69 year-old male, with KRAS-mutated metastatic colorectal cancer. Following a right hemicolectomy and liver/lung metastasectomies, a novel POMK-NRG1 fusion was detected and afatinib initiated (SD, 4 months). Eight months after initiation, afatinib treatment is ongoing, in combination with radiotherapy, with SD. Patient 4, 54 year-old male, with KRAS-wild-type metastatic pancreatic cancer. Following progression on chemotherapy, APP-NRG1 fusion was detected as part of the Personalized Oncogenomics study (NCT02155621), and afatinib initiated; PR is ongoing after 7 months. Conclusions: These findings add to a growing body of evidence that afatinib is a potential treatment option for patients with NRG1+ tumours. Prospective study is ongoing/planned in the Drug Rediscovery Protocol trial (DRUP; NCT02925234) and Targeted Agent and Profiling Utilization Registry study (TAPUR; NCT02693535).
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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 | 0.000 |
| 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) | 0.000 | 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 it