Dermatologic Adverse Events Associated With Use of Adjuvant Lapatinib in Combination With Paclitaxel and Trastuzumab for HER2-Positive Breast Cancer: A Case Series Analysis.
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SUBMITTER: Friedman MD
PROVIDER: S-EPMC5599140 | biostudies-literature | 2016 Jun
REPOSITORIES: biostudies-literature
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Dermatologic Adverse Events Associated With Use of Adjuvant Lapatinib in Combination With Paclitaxel and Trastuzumab for HER2-Positive Breast Cancer: A Case Series Analysis.
Friedman Marissa D MD Lacouture Mario M Dang Chau C
Clinical breast cancer 20151117 3
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Project description:Lapatinib adds to the efficacy of trastuzumab in preclinical models and also in the neo-adjuvant setting. This study assesses the safety and feasibility of adding lapatinib to paclitaxel and trastuzumab (THL) as part of the adjuvant therapy for HER2-positive breast cancer (HER2+ BC). In this single-arm phase II study, patients with stages I-III HER2+ BC received standard anthracycline-based chemotherapy followed by weekly taxane, with concurrent standard trastuzumab, plus daily lapatinib for a total of 12 months. The primary endpoint was symptomatic congestive heart failure, secondary endpoints included overall safety. A total of 109 eligible patients were enrolled. Median follow-up is 4.3 years. No patients experienced congestive heart failure while on treatment. Mean left ventricular ejection fraction at baseline and at the end of THL were 63.6 % (N = 109, SD = 5.7) and 59.8 % (N = 98, SD = 8.1), respectively [mean change -3.95 % (N = 98, SD = 8.3), p < 0.001]. One hundred and two patients initiated post-AC treatment; of them, 31 % experienced grade 3 (no G4) diarrhea with lapatinib at 750 mg/day. The addition of lapatinib to paclitaxel and trastuzumab following AC does not add cardiac toxicity. Lapatinib dose of 750 mg/day in combination with standard chemotherapy plus trastuzumab has acceptable overall tolerability.
| S-EPMC3608861 | biostudies-other
Project description:BackgroundNo single standard treatment exists for patients with small, node-negative, human epidermal growth factor receptor type 2 (HER2)-positive breast cancers, because most of these patients have been ineligible for the pivotal trials of adjuvant trastuzumab.MethodsWe performed an uncontrolled, single-group, multicenter, investigator-initiated study of adjuvant paclitaxel and trastuzumab in 406 patients with tumors measuring up to 3 cm in greatest dimension. Patients received weekly treatment with paclitaxel and trastuzumab for 12 weeks, followed by 9 months of trastuzumab monotherapy. The primary end point was survival free from invasive disease.ResultsThe median follow-up period was 4.0 years. The 3-year rate of survival free from invasive disease was 98.7% (95% confidence interval [CI], 97.6 to 99.8). Among the 12 relapses seen, 2 were due to distant metastatic breast cancer. Excluding contralateral HER2-negative breast cancers and nonbreast cancers, 7 disease-specific events were noted. A total of 13 patients (3.2%; 95% CI, 1.7 to 5.4) reported at least one episode of grade 3 neuropathy, and 2 had symptomatic congestive heart failure (0.5%; 95% CI, 0.1 to 1.8), both of whom had normalization of the left ventricular ejection fraction after discontinuation of trastuzumab. A total of 13 patients had significant asymptomatic declines in ejection fraction (3.2%; 95% CI, 1.7 to 5.4), as defined by the study, but 11 of these patients were able to resume trastuzumab therapy after a brief interruption.ConclusionsAmong women with predominantly stage I HER2-positive breast cancer, treatment with adjuvant paclitaxel plus trastuzumab was associated with a risk of early recurrence of about 2%; 6% of patients withdrew from the study because of protocol-specified adverse events. (Funded by Genentech; ClinicalTrials.gov number, NCT00542451.).
| S-EPMC4313867 | biostudies-literature
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.
| S-EPMC6720931 | biostudies-literature
Project description:BackgroundDual 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 methodsEligible 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%.ResultsFrom 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.ConclusionThe 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.
| S-EPMC4968930 | biostudies-literature
Project description:The excellent outcomes seen in patients treated with adjuvant trastuzumab emtansine (T-DM1) in the ATEMPT trial and the favorable toxicity profile associated with this agent make T-DM1 a potential therapeutic option for select patients with stage I HER2-positive breast cancer. Moreover, T-DM1 is an established adjuvant treatment for patients with HER2-positive breast cancer with the residual invasive disease after neoadjuvant therapy. Given that cardiotoxicity is the most significant adverse event of trastuzumab, which is a main molecular component of T-DM1, we conducted a sub-analysis of the ATEMPT trial to determine the cardiac safety of adjuvant T-DM1. In this analysis, the incidence of grade 3-4 left ventricular systolic dysfunction (LVSD) in T-DM1 or trastuzumab plus paclitaxel arms were respectively 0.8 and 1.8%. In addition, three (0.8%) patients in the T-DM1 arm and six (5.3%) patients in the adjuvant paclitaxel with trastuzumab (TH) arm experienced a significant asymptomatic left ventricular ejection fraction (LVEF) decline that per-protocol required holding T-DM1 or trastuzumab. All patients with available follow-up data experienced full resolution of cardiac symptoms and LVEF normalization. Furthermore, we performed an exploratory analysis to assess the relationship between age, baseline LVEF, and body mass index with cardiac outcomes. No significant association between these baseline characteristics and the incidence of significant asymptomatic LVEF decline or symptomatic LVSD was identified. The low incidence of significant cardiac adverse events in this population during therapy with adjuvant T-DM1 suggests that studies on the cost-effectiveness of cardiac monitoring during adjuvant therapy using anthracycline-free regimens are needed.Clinical Trial Registration: ClinicalTrials.gov, NCT01853748.
| S-EPMC8850608 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-05-08 | GSE130788 | GEO
Project description:Objectives: Adjuvant paclitaxel and trastuzumab has been shown to be an effective regimen with low risk of cancer recurrence and treatment-related toxicities in early-stage node-negative, HER2-positive breast cancer. We investigated the cost-effectiveness of this regimen.Methods: A Markov-based microsimulation model with six health states is used to simulate four adjuvant therapy options for women with early-stage node-negative, HER2-positive breast cancer at different age groups. The four treatment arms are 1) adjuvant paclitaxel and trastuzumab (TH), 2) doxorubicin, cyclophosphamide, paclitaxel and trastuzumab (ACTH), 3) docetaxel, carboplatin and trastuzumab (TCH), and 4) no adjuvant trastuzumab (NT). Data from randomized trials were used to estimate treatment efficacy. Societal perspective was used in this cost-effectiveness analysis. Costs were measured in 2016 US dollars (US$) and quality-adjusted life-years (QALYs) was used for health outcomes. Sensitivity analyses were performed to evaluate the impact of uncertainty in parameter estimation.Results: We found that 40-year-old women undergoing TH treatment would have an average of 16.17 QALYs for the cost of $178,650 when lifetime horizon is used. Compared to NT, TH has incremental cost-effectiveness ratios ranged from $10,584 (ages 40-49) to $84,981 (age 80+) per additional QALYs. The sensitivity analysis showed that TH is cheaper and leads to higher QALYs compared to both ACTH and TCH for all age groups and time horizons.Conclusions: TH is cost-effective for all age groups in the base case scenario and in the sensitivity analysis. In order to reduce the parameter uncertainty, clinical trials with longer follow-up times are needed.
| S-EPMC6550431 | biostudies-literature
Project description:Adjuvant docetaxel, carboplatin, and trastuzumab (TCH) is a standard regimen for HER2+ breast cancer. Dual HER2-blockade with lapatinib (L) and trastuzumab demonstrated significant activity in the metastatic and neoadjuvant settings. This study evaluates neoadjuvant TC plus trastuzumab (H) and/or lapatinib (L). This study demonstrated a similar pCR rate with TCH and TCHL and a lower rate of pCR with TCL. Treatment-related toxicity limited the ability for participants to receive protocol-specified chemotherapy and HER2-targeted therapy in the TCHL Arm.
2019-05-08 | GSE130787 | GEO
Project description:Adjuvant docetaxel, carboplatin, and trastuzumab (TCH) is a standard regimen for HER2+ breast cancer. Dual HER2-blockade with lapatinib (L) and trastuzumab demonstrated significant activity in the metastatic and neoadjuvant settings. This study evaluates neoadjuvant TC plus trastuzumab (H) and/or lapatinib (L). This study demonstrated a similar pCR rate with TCH and TCHL and a lower rate of pCR with TCL. Treatment-related toxicity limited the ability for participants to receive protocol-specified chemotherapy and HER2-targeted therapy in the TCHL Arm.
2019-05-08 | GSE130786 | GEO
Project description:Targeting the epidermal growth factor receptor (egfr) pathway has become standard practice for the treatment of advanced non-small-cell lung cancer. Compared with chemotherapy, egfr tyrosine kinase inhibitors (tkis) have been associated with improved efficacy in patients with an EGFR mutation. Together with the increase in efficacy comes an adverse event (ae) profile different from that of chemotherapy. That profile includes three of the most commonly occurring dermatologic aes: acneiform rash, stomatitis, and paronychia. Currently, no randomized clinical trials have evaluated the treatments for the dermatologic aes that patients experience when taking egfr tkis. Based on the expert opinion of the authors, some basic strategies have been developed to manage those key dermatologic aes. Those strategies have the potential to improve patient quality of life and compliance and to prevent inappropriate dose reductions.
| S-EPMC4399609 | biostudies-literature