CTNI-05. NRG ONCOLOGY / RTOG 1119: PHASE II RANDOMIZED STUDY OF WHOLE BRAIN RADIOTHERAPY / STEREOTACTIC RADIOSURGERY WITH CONCURRENT LAPATINIB IN PATIENTS WITH BRAIN METASTASES FROM HER2-POSITIVE BREAST CANCER
Bibliographic record
Abstract
Abstract Trastuzumab/pertuzumab improved outcomes for patients (pts) with HER2+ breast cancer. Increased survival coupled with limited blood-brain barrier (BBB) penetration of these agents apparently contributes to increased incidence of brain metastases (BM). Lapatinib (L) crosses the BBB and demonstrates activity against BM. Based upon pre/early clinical data, it’s hypothesized that L + whole brain radiotherapy (WBRT) or Stereotactic Radiosurgery (SRS) would improve intracranial control compared to WBRT/SRS (RT) alone. This randomized phase II trial included HER2+ breast cancer pts with ≥ 1 measurable, unirradiated parenchymal BM. Pts were randomized 1:1 to WBRT (37.5 Gy/3 weeks) or SRS +/- concurrent L (1000 mg dailyx6 weeks), andwere stratified by graded prognostic assessment (GPA), use of non-CNS penetrating anti-HER2 therapies, and previous SRS/resection. The primary endpoint was intracranial complete response (CR) rate 12weeks (wk) after RT. Secondary endpoints included objective response rate (ORR), lesion-specific response rate, CNS progression-free survival, and overall survival. 114 of 143 pts were evaluable for 12-wk CR (52 RT, 62 RT+L). Rate of grade 3 and 4 adverse events were 8% and 0% for RT and 29% and 6% for RT+L. 92% and 90% pts received concurrent and adjuvant L per protocol/acceptable variation. There were no significant differences in 12 or 4wk CR rates (p=0.97 and p=0.77); 5.8% and 0% at 12wk and 3.6% and 1.5% at 4wk for RT and RT+L, respectively. The ORR at 4 wk was 42% and 56% (p=0.059, RECIST), 40% and 58% (p=0.027, WHO) in the RT and RT+L, respectively. Although the addition of lapatinib to WBRT/SRS did not improve the 12wk CR rate, it showed meaningful clinical benefit by demonstrating a trend toward improvement of 4 wk ORR. Results of ongoing central review of MRIs using RECIST1.1, WHO and RANO-BM criteria including secondary endpointswill be reported. Support: NCI grants U10CA180868, U10CA180822, UG1CA189867, and Novartis
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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".