Randomized phase II trial of osimertinib with or without local consolidation therapy (LCT) for patients with EGFR-mutant metastatic NSCLC (NORTHSTAR)
Bibliographic record
Abstract
Background: Osimertinib has been shown to be superior to erlotinib or gefitinib in previously untreated patients with EGFR mutant (exon 19 deletion/L858R) NSCLC. Osimertinib is approved for the treatment of patients with metastatic T790M+ NSCLC who have disease progression after EGFR-TKI therapy. The majority of EGFR mutant NSCLC patients who are treated with a TKI ultimately acquire resistance, including those treated with osimertinib. We have recently completed a phase 2 randomized clinical trial demonstrating that patients with oligometastatic NSCLC treated with aggressive local consolidation therapy (surgery or radiation) have improved progression-free survival compared to those patients treated with systemic therapy alone (Gomez et al., Lancet Oncol, 2016). A retrospective review of EGFR-mutant subset of patients enrolled in the trial suggests that EGFR-mutant patients may derive greater benefit from this approach. Thus, two premises underlie the current randomized trial: 1) osimertinib is standard of care for treatment of primary and TKI resistant EGFR-mutant metastatic NSCLC, and 2) the majority of patients treated with osimertinib ultimately become resistant, and LCT has been found to improve outcomes compared to systemic therapy alone. Trial design: A phase 2 randomized, multicenter, study to evaluate the efficacy of osimertinib with or without LCT for patients with EGFR-mutant metastatic NSCLC. Eligible patients include 1) Previously untreated patients with EGFR-mutant NSCLC (L858R or exon 19 deletion) or 2) NSCLC patients with acquired EGFR T790M that was acquired following progression on first or second generation TKI, this subset of patients must have not received prior third generation TKI. Patients who don’t have disease progression after 6-12 weeks of induction osimertinib will be randomized 1:1 to osimertinib continuation or to osimertinib continuation with LCT Primary end point is progression free survival Exploratory biomarkers associated with resistance to osimertinib will be evaluated in tumor tissue and plasma collected at baseline and progression. 140 patients will be enrolled in 5 centers in North America. Clinical trial identification: NCT03410043. Legal entity responsible for the study: UT MD Anderson Cancer Center. Funding: National Comprehensive Cancer Network NCCN, AZ grant. Disclosure: All authors have declared no conflicts of interest.
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.016 | 0.002 |
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".