TCHL - a phase II neo-adjuvant study assessing TCH (docetaxel, carboplatin and trastuzumab) and TCHL (docetaxel, carboplatin, trastuzumab and lapatinib) in HER-2 positive breast cancer patients: a 5-year follow-up with serum biomarker analysis

Abstract

Background: The docetaxel (T), carboplatin (C) and trastuzumab (H) regimen has been used in the (neo-) adjuvant treatment of HER2+ early stage breast cancer (ESBC). Lapatinib (L) a small molecule HER2 antagonist produces clinical responses following H failure.

Methods: We randomly assigned 88 patients with stages Ic-III HER2+ESBC to receive neoadjuvant TCH, TCL or TCHL followed by surgery and 1 year of H. The primary endpoint was pathological complete response (pCR). Secondary objectives were overall and disease-free survival (OS, DFS).

Results: The TCL arm was closed following demonstration of inferiority of L in another trial. The pCR rates for TCH and TCHL were 52.8 and 51.6 (p = 1.0). At a median 4.8 years follow-up, TCHL patients had a significantly superior DFS; however, OS was similar. Prophylactic loperamide reduced the frequency of diarrhoea. Serum biomarker analysis identified a link between high tumour T-cell levels and high red blood cell, haematocrit, and haemoglobin following commencement of therapy.

Interpretation: The study did not meet its primary endpoint of superior pCR. TCHL produced a significant improvement in DFS. Our study and others suggest a possible role for L in neoadjuvant therapy of HER2+ ESBC.

Clinical trial registration: NCT01485926.

Figure 1

Participant flow chart: populations added. ITT: Intent to Treat; SS: Safety Set.

Figure 2

Kaplan-Meier survival analysis for (A) Disease-free survival (DFS) and (B) Overall survival (OS) for TCH (n = 38) (Green Line), TCHL (n = 37) (Red Line) and TCL (n = 12) (Blue Line) arms of TCHL study.