Intracranial activity of sotorasib vs docetaxel in pretreated KRAS G12C-mutated advanced non-small cell lung cancer from a global, phase 3, randomized controlled trial
Bibliographic record
Abstract
OBJECTIVES: To assess the efficacy and safety of sotorasib in patients with brain metastases using data from the phase 3 CodeBreaK 200 study, which evaluated sotorasib in adults with pretreated advanced or metastatic KRAS G12C-mutated non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients with KRAS G12C-mutated NSCLC who progressed after platinum-based chemotherapy and checkpoint inhibitor therapy were randomized 1:1 to sotorasib or docetaxel. An exploratory post-hoc analysis evaluated central nervous system (CNS) progression-free survival (PFS) and time to CNS progression in patients with treated and stable brain metastases at baseline. Measures were assessed by blinded independent central review per study-modified Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria. RESULTS: Of the patients randomly assigned to receive sotorasib (n=171) or docetaxel (n=174), baseline CNS metastases were present in 40 (23%) and 29 (17%) patients, respectively. With a median follow-up of 20.0 months for this patient subgroup, median CNS PFS was longer with sotorasib compared with docetaxel (9.6 vs 4.5 months; hazard ratio, 0.43 [95% CI, 0.20-0.92]; P=0.02). Among patients with baseline treated CNS lesions of ≥10 mm, the percentage of patients who achieved CNS tumor shrinkage of ≥30% was two-fold higher with sotorasib than docetaxel (33.3% vs 15.4%). Treatment-related adverse events among patients with CNS lesions at baseline were consistent with those of the overall study population. CONCLUSIONS: These results suggest intracranial activity with sotorasib complements the overall PFS benefit observed with sotorasib vs docetaxel, with safety outcomes similar to those in the general CodeBreaK 200 population. CLINICAL TRIALS REGISTRATION NUMBER: NCT04303780.
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How this classification was reachedexpand
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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| 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) | 0.001 | 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 teacher head, 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".