De-escalated neoadjuvant taxane plus trastuzumab and pertuzumab with or without carboplatin in HER2-positive early breast cancer (neoCARHP): A multicentre, open-label, randomised, phase 3 trial.

Abstract

LBA500 Background: Neoadjuvant taxane, carboplatin and trastuzumab plus pertuzumab is associated with excellent treatment outcomes. The neoCARHP study aimed to evaluate the efficacy and safety of a de-escalated neoadjuvant taxane plus trastuzumab and pertuzumab with or without carboplatin in HER2-positive early breast cancer. Methods: The neoCARHP was a multicenter, open-label, randomized non-inferiority phase 3 trial conducted in 15 hospitals. Eligible patients were ≥18 years old with untreated, stage II-III, invasive HER2-positive breast cancer. Patients were stratified by nodal and hormone receptor status and randomized (1:1) to receive six 3-week cycles of an investigator-selected taxane (docetaxel, paclitaxel or nab-paclitaxel) plus trastuzumab (8 mg/kg loading dose, then 6 mg/kg every 3 weeks) and pertuzumab (840 mg loading dose, then 420 mg every 3 weeks), with carboplatin (TCbHP; AUC 6 mg/mL per min) or without carboplatin (THP). The primary endpoint was the pathological complete response (pCR) rate in the breast and axilla (ypT0/is ypN0), assessed in the modified intent-to-treat (mITT) population (all randomised patients who received at least one dose of study medication). The primary efficacy analysis was performed using the Cochran-Mantel-Haenszel χ 2 test(stratified by nodal and hormone receptor status), with a prespecified non-inferiority margin of -10%. Assuming a pCR rate of 62.8% for each group, 774 patients would provide 80% power at a one-sided significance level of 0.025, with an assumed 5% dropout rate. Safety was assessed in all patients who received the study drug. The trial is registered with ClinicalTrials.gov (NCT04858529), and adjuvant phase follow-up is ongoing. Results: Between April 30, 2021, and August 27, 2024, 774 patients were enrolled and randomized (387 per group), with 766 included in the mITT population (382 in THP and 384 in TCbHP). 245 (64.1% [95% CI 59.2-68.8]) patients in the THP group achieved pCR, compared with 253 (65.9% [61.0-70.5]) patients in the TCbHP group (absolute difference -1.8%, 95% CI -8.5 to 5.0; odds ratio 0.93, 95% CI 0.69 to 1.25; p=0.0089). Patients receiving THP had fewer grade 3–4 adverse events (79 of 382 [20.7%] vs 133 of 384 [34.6%]) and serious adverse events (5 of 382 [1.3%] vs 18 of 384 [4.7%]) compared with those receiving TCbHP. The most common grade 3-4 adverse events with THP were neutropenia (26 of 382 [6.8%] vs 63 of 384 [16.4%] with TCbHP), leukopenia (21 [5.5%] vs 57 [14.8%]) and diarrhoea (10 [2.6%] vs 16 [4.2%]). No treatment-associated deaths occurred. Conclusions: THP provided non-inferior pCR rates and improved tolerability compared with TCbHP. Omitting carboplatin could be an efficacious de-escalated neoadjuvant strategy in the presence of dual HER2 blockade for patients with HER2-positive early breast cancer. Clinical trial information: NCT04858529 .