Sunitinib (SU) in Combination with Trastuzumab (T) for the Treatment of Advanced Breast Cancer (ABC): Activity and Safety Results from a Phase II Study.
Bibliographic record
Abstract
Abstract Background: SU is an oral, multitargeted tyrosine kinase inhibitor of VEGFRs, PDGFRs, KIT, RET, FLT3, and CSF-1R, with single-agent activity in patients (pts) with heavily pretreated ABC (locally recurrent or metastatic breast cancer). T is approved for 2nd-line monotherapy and in combination with taxane-based therapies for 1st-line ABC. The combination of SU + T in HER2+ ABC pts was investigated.Materials and methods: Eligible pts with HER2+ ABC received a starting dose of oral SU 37.5 mg/d (continuous daily dosing [CDD]) and either T administered wkly (iv loading 4 mg/kg then wkly 2 mg/kg) or q3w (loading 8 mg/kg then q3w 6 mg/kg). Due to changing standard of care, the trial was amended to include pts having prior chemotherapy in the 1st-line setting. Previous treatment (tx) with T (± lapatinib) was permitted. The primary endpoint was objective response rate (ORR). Secondary endpoints included safety, progression-free survival (PFS), pharmacokinetics (PK) and quality of life (QoL).Results: As of April 2009, 60 pts were enrolled (6 on the original protocol and 54 under the amendment). Of 54 pts enrolled post-amendment, 6 pts continue on study and 48 have discontinued, 12 due to AEs. Most (n=31; 57%) pts received SU + T as 1st-line tx and 11/31 pts were completely tx-naïve. Pts received a median of 5 cycles (range: 1–16) of SU and 4 cycles (range: 1–15) of T. SU was dose reduced from 37.5 mg/d to 25 mg/d in 39% of pts. All pts were evaluable for safety and 52 pts were evaluable for efficacy. ORR was 34.6% and clinical benefit rate was 48% (2 CR; 16 PR; 7 SD ≥24 wks). Of the 18 responders, 5 pts were completely tx-naïve and 9 pts were 1st-line. Median PFS was 25.3 wks (95% CI, 19.3, 29.1). Most AEs were G1/2. G3 non-hematologic AEs in ≥10% pts were asthenia (17%) and hypertension (11%) and 3 G4 events occurred (LVEF decline, pulmonary embolism, and pancreatitis). Hematologic AEs (G3/4 in ≥10% pts) were neutropenia (22%) and thrombocytopenia (17%). One G5 event (cardiogenic shock) was reported. LVEF decline/LV dysfunction occurred in 21 pts (6 pts had ≥G3 AEs); 18/21 pts (86%) had received prior anthracycline and 12 pts (57%) prior T. There was no significant on-tx change from baseline in the QoL domain. Mean (SD) steady state level for SU was 46.1 (25.9) ng/mL in agreement with prior observations.Conclusions: The combination of SU (37.5 mg/d; CDD schedule) + T (wkly or q3w) showed acceptable tolerability and antitumor activity in HER2+ ABC pts without adversely affecting overall QoL. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 201.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".