Survival after neoadjuvant therapy with trastuzumab-lapatinib plus chemotherapy

Survival data from 4 randomised studies of the tyrosine kinase inhibitor lapatinib in combination with neoadjuvant trastuzumab versus trastuzumab (plus anthracycline or paclitaxel chemotherapy) in patients with HER2-positive early breast cancer showed that patients who achieved a pathological complete response (pCR) had a reduced risk of relapse by 65% in patients with hormone receptor-negative tumours and by 40% in patients with hormone receptor-positive disease.

The optimal selection of patients with HER2-positive early breast cancer who may benefit most from de-escalation of treatment remains an unmet need. Prof. Valentina Guarneri (University of Padua, Italy) pointed out that although all studies reported improved outcomes if patients achieved pCR, survival data were not conclusive in any of the individual studies [1]. To address this gap, Prof. Guarneri and colleagues performed a meta-analysis of 4 randomised phase 2 and 3 studies (CALGB40601 [2], CHER-Lob [3], NSABP B-41 [4], NeoALTTO [5]) testing lapatinib in combination with neoadjuvant trastuzumab plus chemotherapy for HER2-positive early breast cancer.

In total, the survival data from 1,410 patients were included in the analysis derived from these 4 studies. Adding lapatinib to trastuzumab improved overall survival (OS) by 35% (HR 0.65; 95% CI 0.43‒0.98). In addition, relapse-free survival (RFS) was longer with the combination of lapatinib than with trastuzumab only (HR 0.62; 95% CI 0.46‒0.85).

Achievement of a pCR is strongly prognostic for superior outcomes in HER-positive early breast cancers. For all treatments, patients achieving a pCR had better RFS and OS than those with residual disease at surgery (HR 0.45; 95% CI 0.34‒0.60 for RFS and HR 0.34; 95% CI 0.23‒0.51 for OS). When the researchers stratified the patients who achieved pCR by their tumour’s HR status, HR-negative status was associated with a 65% reduction of risk of relapse (HR 0.35; 95% CI 0.23‒0.53) and a 73% reduction of risk of death (HR 0.27; 95% CI 0.15‒0.47). Patients with HR-positive tumours also had improved RFS (HR 0.60; 95% CI 0.37‒0.97), but the benefit was smaller than in patients with HR-negative disease.

In conclusion, these data indicate that neoadjuvant lapatinib-trastuzumab in early HER2-positive breast cancers does provide improved survival outcomes. Furthermore, patients on any treatment who achieve pCR, especially those with HR-negative tumours, may be eligible candidates for treatment de-escalation.

1. Guarneri V, et al. Survival after neoadjuvant therapy with trastuzumab-lapatinib and chemotherapy in patients with HER2-positive early breast cancer: A meta-analysis of randomised trials. Abstract 117O, ESMO Congress 2021, 16–21 September.
2. Fernandez-Martinez A, et al. J Clin Oncol. 2020;38(35):4184-4193.
3. Guarneri V, et al. Eur J Cancer. 2021;153:133-141.
4. Robidoux A, et al. Lancet Oncol. 2013;14(12):1183-92.
5. Venet D, et al. Clin Cancer Res. 2021;27:5607-18.

 

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Posted on 19 November, 202129 February, 2024