Abstract GS1-02: NSABP B-47 (NRG oncology): Phase III randomized trial comparing adjuvant chemotherapy with adriamycin (A) and cyclophosphamide (C) → weekly paclitaxel (WP), or docetaxel (T) and C with or without a year of trastuzumab (H) in women with node-positive or high-risk node-negative invasive breast cancer (IBC) expressing HER2 staining intensity of IHC 1+ or 2+ with negative FISH (HER2-Low IBC)
Bibliographic record
Abstract
Abstract Background: Adjuvant trastuzumab (H) reduces cancer recurrence and improves survival in patients (pts) with HER2-amplified or overexpressing (IHC 3+ staining intensity) IBC. Two of the landmark trials that demonstrated the efficacy of H-based eligibility on HER2 testing performed at local site laboratories were found to contain a cohort of pts without amplification or IHC overexpression on tissue submitted for central testing. These HER2-low cohorts appeared to benefit from the addition of H, and efforts at external HER2 testing validation and laboratory explorations did not negate these findings. NSABP B-47 was performed to determine if these findings would be confirmed in a large prospective randomized trial. The primary aim was to determine whether the addition of H to chemotherapy (CT) regimens of AC→WP or TC (choice per investigator discretion) would improve invasive disease-free survival (IDFS). Methods: From 2/8/2011 to 2/10/2015, 3270 women were enrolled with 1630 pts randomly assigned to Arm 1 [TC: docetaxel 75mg/m2, cyclophosphamide 600 mg/m2 every 3 weeks x 6 cycles; or AC→WP: doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 2 or 3 weeks x 4 cycles followed by paclitaxel 80 mg/m2 every week x 12], and 1640 pts to Arm 2 [same CT regimens + 12 months of H]. Pts were stratified by IHC score (1+ vs 2+), number of positive nodes (0-3, 4-9, ≥10), hormone receptor status (ER or PgR positive vs both negative), and CT (TC vs AC→WP). Overall 58.5% were ≥50 years, 57% had tumors with IHC 1+, 17.3% were ER- and PgR-, 19.9% were node negative, and 27.4% had ≥4 positive nodes. TC was the intended CT regimen for 44.2%. Results: As of 7/31/2017, the median follow-up time was 46.1 months. We observed 264 IDFS events, which triggered the definitive analysis for the primary endpoint. The addition of H to CT showed a 5-year IDFS of 89.6% compared to 89.2% for CT alone (HR 0.98; 95%CI 0.77-1.26; P=0.90). The findings did not differ by level of HER2 IHC expression, level of lymph node involvement, or hormone receptor status. 5-year point estimates for RFI were 92.0% for CT+H compared to 92.2% for CT alone (HR 0.995; 95%CI 0.75-1.32; P=0.97). 5-year estimates for DRFI were 92.7% for CT+H and 93.5% for CT alone (HR 1.10; 95%CI 0.81-1.49; P=0.55). The addition of H did not change OS significantly with 5-year point estimates of 94.8% in CT+H vs 96.2% in CT alone (HR 1.33; 95%CI 0.91-1.94; P=0.14). 4.3% of women in the CT arm experienced Grade 4 or 5 toxicities compared to 5.0% in CT+H. Conclusion: The addition of H to CT did not demonstrate a reduction in IDFS, RFI, or DRFI in women with non-overexpressing but IHC measurable HER2 IBC. This prospective study did not confirm the retrospective findings in NSABP B-31 or N9831. The threshold of HER2 expression or genetic amplification for H benefit remains unchanged. Support: NCI U10-180868, -180822, -44066, UG1-189867, and Genentech, Inc. Citation Format: Fehrenbacher L, Cecchini RS, Geyer CE, Rastogi P, Costantino JP, Atkins JN, Polikoff J, Boileau J-F, Provencher L, Stokoe C, Moore TD, Robidoux A, Borges V, Albain KS, Swain SM, Paik S, Mamounas EP, Wolmark N. NSABP B-47 (NRG oncology): Phase III randomized trial comparing adjuvant chemotherapy with adriamycin (A) and cyclophosphamide (C) → weekly paclitaxel (WP), or docetaxel (T) and C with or without a year of trastuzumab (H) in women with node-positive or high-risk node-negative invasive breast cancer (IBC) expressing HER2 staining intensity of IHC 1+ or 2+ with negative FISH (HER2-Low IBC) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS1-02.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.004 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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 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".