Neoadjuvant pegylated liposomal doxorubicin-containing chemotherapy in combination with trastuzumab and pertuzumab in patients with HER2-positive early breast cancer: A randomized phase II study (METIS).
Bibliographic record
Abstract
596 Background: In the neoadjuvant phase, anti-HER2 therapy is usually delayed when combined with anthracycline-containing chemotherapy regimens, since conventional anthracycline and anti-HER2 agents cannot be given simultaneously. Pegylated liposomal doxorubicin (PLD) is a modified form of doxorubicin that can lower the risk of heart damage while preserving its anticancer activity. In this study, we aimed to explore whether PLD could replace conventional anthracycline and be used earlier with anti-HER2 agents to enhance neoadjuvant efficacy without increasing cardiotoxicity. Methods: The METIS study was an investigator-initiated, multicenter, open-label, randomized, phase II study conducted at 11 centers in China. Patients aged 18 to 70 years old with previously untreated stage II–III histologically documented HER2-positive breast cancer were randomly assigned (1:1) to receive PLD-containing or epirubicin-containing neoadjuvant chemotherapy. The PLD-containing regimen consisted of 4 cycles of PLD (35 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks, followed by 4 cycles of a taxane of the investigator's choice (docetaxel, paclitaxel, or nab-paclitaxel). The epirubicin-containing regimen consisted of 4 cycles of epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) every 3 weeks, followed by 4 cycles of a taxane of the investigator's choice. Both regimens included trastuzumab (8 mg/kg loading dose, then 6 mg/kg maintenance dose) and pertuzumab (840 mg loading dose, then 420 mg maintenance dose) every 3 weeks. Trastuzumab and pertuzumab were given with all chemotherapy cycles in the PLD-containing group, and with the taxane cycles only in the epirubicin-containing group. The primary end point was investigator-assessed total pathological complete response (tpCR) rate in the intention-to-treat population. Results: From August 2019 to March 2023, 156 were enrolled and randomly assigned to receive PLD-containing (n=80) or epirubicin-containing (n=76) treatment. At date of data analysis, the median follow-up duration was 16.3 months. The PLD-containing treatment group had a higher rate of pathological complete response (67.5%, 95% CI 56.1-77.6) than the epirubicin-containing group (48.7%, 95% CI 37.0-60.4), with a rate difference of 18.8% (p=0.033). Only one patient in the epirubicin-containing group experienced a grade 3 decrease in left ventricular ejection fraction, while none did in the PLD-containing group. Other adverse events were similar in both groups. Conclusions: A combination of PLD and cyclophosphamide with trastuzumab and pertuzumab, followed by a taxane, trastuzumab, and pertuzumab, significantly increased the rate of tpCR without more cardiotoxicity in neoadjuvant treatment for early-stage HER2-positive breast cancer patients. Clinical trial information: NCT04172259 .
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.001 | 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 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".