Messaggi chiave
- HELEN-006 è uno studio multicentrico, randomizzato, di fase III, che si è proposto di valutare l’efficacia di nab-paclitaxel settimanale rispetto al regime standard carboplatino-docetaxel, entrambi associati a trastuzumab e pertuzumab, nel trattamento neoadiuvante di pazienti con carcinoma mammario HER2+ in stadio II-III. Si presenta di seguito l’analisi finale degli esiti di risposta patologica completa (pCR), l’endpoint primario dello studio.
- È stato arruolato un totale di 689 pazienti. A un follow-up mediano di 26 mesi, il tasso di pCR è risultato pari al 66,3 vs 57,6% nel gruppo sperimentale rispetto ai controlli (odds ratio combinato, 1,54; IC 95%, 1,10-2,14; p stratificata = 0,011). Il 30% delle pazienti trattate con nab-paclitaxel ha manifestato eventi avversi (EA) di grado 3-4, rispetto al 38% delle pazienti nel gruppo carboplatino-docetaxel. Gli EA G3-4 più comuni sono stati nausea (7 vs 23%), diarrea (8 vs 16%) e neuropatia (13 vs 2%). EA seri correlati al trattamento sono stati segnalati rispettivamente in tre e cinque pazienti, senza alcun decesso osservato.
- I risultati presentati suggeriscono una possibile superiorità di nab-paclitaxel in combinazione con trastuzumab e pertuzumab rispetto allo standard di cura nel trattamento neoadiuvante di pazienti con carcinoma mammario precoce HER2+. È in corso il follow-up della fase adiuvante.
Abstract
Background
- A previous phase 2 trial showed promising outcomes for patients with HER2-positive early-stage breast cancer using neoadjuvant de-escalation chemotherapy with paclitaxel, trastuzumab, and pertuzumab.
- We aimed to evaluate the efficacy of weekly nab-paclitaxel compared with the standard regimen of docetaxel plus carboplatin, both with trastuzumab and pertuzumab, as neoadjuvant therapies for patients with HER2-positive breast cancer.
Methods
- HELEN-006 was a multicentre, randomised, phase 3 trial done at six hospitals in China.
- We enrolled patients aged 18-70 years with untreated, histologically confirmed stage II-III invasive HER2-positive breast cancer and an Eastern Cooperative Oncology Group performance status of 0 or 1.
- Using an interactive response system, patients were randomly assigned (1:1) under a permuted block randomisation scheme (block size of four), stratified by tumour stage, nodal status, and hormone receptor status.
- Patients received either intravenous nab-paclitaxel (125 mg/m2 on days 1, 8, and 15) for six 3-week cycles, or intravenous docetaxel (75 mg/m2 on day 1) plus intravenous carboplatin (area under the concentration-time curve 6 mg/mL per min on day 1) for six 3-week cycles.
- Both groups also received concurrent intravenous trastuzumab, with an initial loading dose of 8 mg/kg and a maintenance dose of 6 mg/kg on day 1, as well as intravenous pertuzumab with a loading dose of 840 mg and a maintenance dose of 420 mg on day 1.
- This report is the final analysis of the primary endpoint, pathological complete response (ypT0/is ypN0), analysed in all patients who started treatment (modified intention to treat).
- The trial is registered with ClinicalTrials.gov, NCT04547907, and follow-up of the adjuvant phase is ongoing.
Findings
- Between Sept 20, 2020, and March 1, 2023, 789 patients were screened for eligibility, 689 of whom were randomly assigned (343 to the nab-paclitaxel group and 346 to the docetaxel plus carboplatin group).
- All 689 patients were Asian women.
- 669 patients received at least one dose of the study treatment and were included in the full analysis set (332 in the nab-paclitaxel group and 337 in the docetaxel plus carboplatin group).
- Median age of the patients was 50 years (IQR 43-55).
- Median follow-up time was 26 months (IQR 19-32).
- 220 (66·3% [95% CI 61·2-71·4]) patients in the nab-paclitaxel group had a pathological complete response, compared with 194 (57·6% [52·3-62·9]) in the docetaxel plus carboplatin group (combined odds ratio 1·54 [95% CI 1·10-2·14]; stratified p = 0·011).
- 100 (30%) patients in the nab-paclitaxel group and 128 (38%) in the docetaxel plus carboplatin group had grade 3-4 adverse events.
- The most common grade 3-4 adverse events were nausea (22 [7%] in the nab-paclitaxel group vs 76 [23%] in the docetaxel plus carboplatin group), diarrhoea (25 [8%] vs 55 [16%]), and neuropathy (43 [13%] vs eight [2%]).
- Serious drug-related adverse events were reported in three (1%) patients in the nab-paclitaxel group and five (2%) in the docetaxel plus carboplatin group.
- No treatment-related deaths were reported in either group.
Interpretation
- These findings might suggest a potential advantage of nab-paclitaxel combined with trastuzumab and pertuzumab compared with the standard regimen in neoadjuvant therapy for patients with HER2-positive early breast cancer, suggesting that this new combination might establish a new standard for neoadjuvant treatment in this patient population.