117O - Survival after neoadjuvant therapy with trastuzumab-lapatinib and chemotherapy in patients with HER2-positive early breast cancer: A meta-analysis of randomised trials

Background

Studies testing addition of lapatinib (L) to neoadjuvant trastuzumab (T) plus chemotherapy reported an increase in pathologic complete response (pCR) rates but were discordant on the effect of treatment on survival, mainly due to suboptimal power. We here leverage the meta-analytic approach to resolve these inconsistencies.

Methods

We conducted a meta-analysis to combine findings from published or unpublished randomised phase 2 and 3 studies testing L in combination with neoadjuvant T plus chemotherapy for HER2+ early breast cancer. Pooled hazard ratios (HRs) were obtained for the effect of L plus T compared to T only, pCR compared to no pCR in the whole study populations, and pCR compared to no pCR in the hormone receptor-negative or positive cohorts.

Results

The meta-analysis included four studies (CALGB40601, CHER-LOB, NSABP-B41, NeoALTTO) for an overall population of 1410 patients. Patients received either T and L or T alone, in combination with paclitaxel or anthracyclines. Relapse-free survival (RFS) was higher with the combination of L plus T than with T only (HR 0.62, 95% CI 0.46-0.85). Dual blockade also led to improved overall survival (OS) (HR 0.65, 95% CI 0.43-0.98). For all treatments combined, 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, and HR 0.34, 95% CI 0.23-0.51, for RFS and OS, respectively). In patients with hormone receptor-negative tumours, pCR 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 hormone receptor-positive tumours also had improved RFS if they achieved pCR (HR 0.60, 95% CI 0.37-0.97), but the benefit was smaller than in hormone receptor-negative disease.

Conclusions

These findings further validate the role of pCR as a strong predictor of outcome in patients with HER2+, especially in hormone receptor-negative disease. Moreover, we here provide robust evidence that dual blockade with L in combination with T and chemotherapy prolongs overall survival, suggesting that L could be repurposed in early settings.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

University of Padua - Department of Surgery, Oncology and Gastroenterology.

Funding

University of Padua – Department of Surgery, Oncology and Gastroenterology: BIRD 2019 (to VG, MVD, PFC) and BIRD 2020 (to VG, MVD, GG).

Disclosure

V. Guarneri: Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Principal Investigator, Local PI: AstraZeneca; Financial Interests, Institutional, Principal Investigator, Local PI: BMS; Financial Interests, Institutional, Principal Investigator, Local PI: Eli Lilly; Financial Interests, Institutional, Principal Investigator, Local PI: MSD; Financial Interests, Institutional, Principal Investigator, Local PI: Novartis; Financial Interests, Institutional, Principal Investigator, Local PI: Roche; Financial Interests, Institutional, Principal Investigator, Local PI: Synton Biopharmaceuticals .G. Griguolo: Other, Other, Travel Support: Novartis; Other, Other, Travel Support: Amgen; Other, Other, Trave Support: Pfizer; Other, Other, Travel Support: Daiichi Sankyo. P.F. Conte: Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Tesaro; Financial Interests, Personal, Other, Honoraria: BMS; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Eli Lilly; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Merck-KGa; Financial Interests, Institutional, Research Grant: Italian Ministry of Health; Financial Interests, Institutional, Research Grant: Veneto Secretary; Financial Interests, Institutional, Research Grant: University of Padua. M.V. Dieci: Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Genomic Health; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Celgene. All other authors have declared no conflicts of interest.