Dataset Information

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.

SUBMITTER: Iyengar NM

PROVIDER: S-EPMC4968930 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Iyengar Neil M NM Fornier Monica N MN Sugarman Steven M SM Theodoulou Maria M Troso-Sandoval Tiffany A TA D'Andrea Gabriella M GM Drullinsky Pamela R PR Gajria Devika D Goldfarb Shari B SB Comen Elizabeth A EA Lake Diana E DE Modi Shanu S Traina Tiffany A TA Lacouture Mario E ME Chen Melanie F MF Patil Sujata S Baselga José J Norton Larry L Hudis Clifford A CA Dang Chau T CT

Clinical breast cancer 20150925 2

<h4>Background</h4>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).<h4>Patients and methods</h4>Eligible patients had HER2-positive breast cancer, tumor size ≤ 3 cm, and negative nodes. Treatment included paclitaxel (175 mg/m(2) × 4, every 2 w ...[more]

PMID: 26454612

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Project description:BackgroundNeoadjuvant dual human epidermal growth factor receptor (HER2) blockade with trastuzumab and pertuzumab plus paclitaxel leads to an overall pathologic complete response (pCR) rate of 46%. Dual HER2 blockade with ado-trastuzumab emtansine (T-DM1) and lapatinib plus nab-paclitaxel has shown efficacy in patients with metastatic HER2-positive breast cancer. To test neoadjuvant effectiveness of this regimen, an open-label, multicenter, randomized, phase II trial was conducted comparing T-DM1, lapatinib, and nab-paclitaxel with trastuzumab, pertuzumab, and paclitaxel in patients with early-stage HER2-positive breast cancer.MethodsStratification by estrogen receptor (ER) status occurred prior to randomization. Patients in the experimental arm received 6 weeks of targeted therapies (T-DM1 and lapatinib) followed by T-DM1 every 3 weeks, lapatinib daily, and nab-paclitaxel weekly for 12 weeks. In the standard arm, patients received 6 weeks of trastuzumab and pertuzumab followed by trastuzumab weekly, pertuzumab every 3 weeks, and paclitaxel weekly for 12 weeks. The primary objective was to evaluate the proportion of patients with residual cancer burden (RCB) 0 or I. Key secondary objectives included pCR rate, safety, and change in tumor size at 6 weeks. Hypothesis-generating correlative assessments were also performed.ResultsThe 30 evaluable patients were well-balanced in patient and tumor characteristics. The proportion of patients with RCB 0 or I was higher in the experimental arm (100% vs. 62.5% in the standard arm, p = 0.0035). In the ER-positive subset, all patients in the experimental arm achieved RCB 0-I versus 25% in the standard arm (p = 0.0035). Adverse events were similar between the two arms.ConclusionIn early-stage HER2-positive breast cancer, the neoadjuvant treatment with T-DM1, lapatinib, and nab-paclitaxel was more effective than the standard treatment, particularly in the ER-positive cohort.Trial registrationClinicaltrials.gov NCT02073487 , February 27, 2014.

Project description:IntroductionTrastuzumab, as the gold standard for HER2-positive BC treatment, was the first-line HER2 targeted drug. However, some studies reported patients benefited more from lapatinib and lapatinib plus trastuzumab therapy than standard trastuzumab therapy. This study presents an update of a systematic review and meta-analysis involving comparison of lapatinib and lapatinib plus trastuzumab therapy versus trastuzumab therapy.AimWe determined whether trastuzumab plus lapatinib or lapatinib therapy is not inferior to trastuzumab therapy in HER2-positive breast cancer patients.MethodsRelevant trials were searched in CNKI, Wanfang, VIP, Sinomed, PubMed, Embase, and Cochrane CENTRAL databases from inception until October 25, 2021. Primary outcomes were OS, DFS/EFS, and PFS while secondary outcomes were pCR (ypT0/is ypN0), pCR (ypT0/is ypN0/+), ORR, DCR, rate of BCS, RFS, cardiac toxicities, and other toxicities.ResultsThirteen randomized controlled trials were included in this study. Trastuzumab combined with lapatinib therapy was found to be superior to standard trastuzumab therapy alone with regard to overall survival, disease-free survival/event-free survival, pathologic complete response (ypT0/is ypN0), pathologic complete response (ypT0/is ypN0/+), recurrence-free survival, higher incidences of diarrhea, and rash/skin toxicity. Lapatinib therapy was established to be inferior to trastuzumab therapy in overall survival, progression-free survival, disease-free survival/event-free survival, pathologic complete response (ypT0/is ypN0) and pathologic complete response (ypT0/is ypN0/+), diarrhea, and rash/skin toxicity and had a low incidence of left ventricular ejection fraction decline.ConclusionsThe efficacy of trastuzumab combined with lapatinib therapy is superior to standard trastuzumab therapy alone; however, it has more non-cardiac grade III/IV toxicities. Moreover, the efficacy of lapatinib therapy is inferior to that of standard trastuzumab therapy alone.

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Dataset Information

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

Background

Patients and methods

Results

Conclusion

Publications

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

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