A Pilot Study of Dose-Dense Paclitaxel With Trastuzumab and Lapatinib for Node-negative HER2-Overexpressed Breast Cancer

Abstract

Background: Dual anti-HER2 therapy is effective for HER2-amplified breast cancer. Weekly paclitaxel, trastuzumab, and full-dose lapatinib (PTL) is not feasible because of grade 3 diarrhea. We conducted a phase II feasibility study of dose-dense (DD; every other week) PTL (ClinicalTrials.gov identifier, NCT01827163).

Patients and methods: Eligible patients had HER2-positive breast cancer, tumor size ≤ 3 cm, and negative nodes. Treatment included paclitaxel (175 mg/m(2) × 4, every 2 weeks with pegfilgrastim), trastuzumab (4 mg/kg load and then 2 mg/kg weekly), and lapatinib (1000 mg daily). After paclitaxel × 4, trastuzumab (6 mg/kg every 3 weeks) plus lapatinib were continued for 1 year. The primary endpoint was feasibility, defined as (1) > 80% of patients completing PTL without a dose delay or reduction, (2) grade 3 diarrhea rate < 20%, and (3) cardiac event rate < 4%.

Results: From May 2013 to November 2013, we enrolled 20 of 55 planned patients. The median age was 49 years (range, 34-74 years). One patient had immediate paclitaxel hypersensitivity and was deemed inevaluable. Only 13 of 19 evaluable patients (68%) completed PTL without a dose delay or reduction or unacceptable toxicities. Only 3 of 19 (16%) had grade 3 diarrhea. Rash was frequent, with all grades in 18 of 19 (95%) and grade 3 in 2 of 19 (11%). The study was stopped early because of excess toxicity.

Conclusion: The discontinuation rate during DD PTL was high, owing, in part, to an unexpectedly high incidence of rash. The trial was halted, because the initial discontinuation rate from overall toxicity made it unlikely that full accrual would demonstrate feasibility.

Keywords: ALTTO; Dose schedule; Dose-dense chemotherapy; Drug toxicity; Taxane.

Copyright © 2016 Elsevier Inc. All rights reserved.

Figures

Figure 1. Treatment Schema. Complete Blood Count Every 2 Weeks During Paclitaxel, Trastuzumab, and Lapatinib (PTL); Liver Function Test Every 2 Weeks During PTL and Every 3 to 6 Weeks During Trastuzumab and Lapatinib; Magnesium and Potassium Levels Every 2 Weeks During PTL and Every 3 to 6 Weeks During Trastuzumab and Lapatinib; Cardiac Biomarkers Including Troponin I, B-natriuretic Peptide, and Neuregulin-1β Every 2 Weeks During PTL Phase (Before and After Infusion) and at Months 6, 9, and 18; Electrocardiogram (EKG) and Multigated Acquisition Scan at Baseline and Months 2, 6, 9, and 18

Abbreviation: ECHO = echocardiogram.

Figure 2. Consolidated Standards of Reporting Trials Diagram

Abbreviations: G = grade; L = lapatinib; PTL = paclitaxel, trastuzumab, and lapatinib; T = trastuzumab.