Abstract P5-21-07: Phase II study of eribulin in combination with pertuzumab plus trastuzumab for human epidermal growth factor receptor 2 (HER2)-positive advanced or metastatic breast cancer

2018 ◽  
Author(s):  
H Kawaguchi ◽  
T Yamashita ◽  
N Masuda ◽  
M Kitada ◽  
K Narui ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Metastatic Breast Cancer ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Phase Ii Study ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Her2 Positive ◽  
Epidermal Growth

Randomized Trial of Lapatinib Versus Placebo Added to Paclitaxel in the Treatment of Human Epidermal Growth Factor Receptor 2–Overexpressing Metastatic Breast Cancer

2013 ◽  
Vol 31 (16) ◽  
pp. 1947-1953 ◽  
Author(s):  
Zhongzhen Guan ◽  
Binghe Xu ◽  
Michelle L. DeSilvio ◽  
Zhenzhou Shen ◽  
Wichit Arpornwirat ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Metastatic Breast Cancer ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Her2 Positive ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth

Purpose Lapatinib is an oral small-molecule tyrosine kinase inhibitor of both epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2). This study is designed to test whether the addition of lapatinib to paclitaxel improves overall survival (OS) compared with placebo plus paclitaxel in patients with HER2-overexpressing metastatic breast cancer (MBC). Patients and Methods This phase III, randomized, double-blind study assessed the efficacy and safety of lapatinib plus paclitaxel compared with placebo plus paclitaxel in patients with newly diagnosed HER2-positive MBC. The primary end point was OS. Secondary end points included progression-free survival (PFS), overall response rate (ORR), clinical benefit rate, and safety. Results The addition of lapatinib to paclitaxel significantly improved OS versus paclitaxel (treatment hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.94; P = .0124); median OS was 27.8 versus 20.5 months, respectively. Median PFS was prolonged by 3.2 months, from 6.5 months with placebo plus paclitaxel to 9.7 months with lapatinib plus paclitaxel (HR, 0.52; 95% CI, 0.42 to 0.64; stratified log-rank P < .001). ORR was significantly higher with lapatinib plus paclitaxel compared with placebo plus paclitaxel (69% v 50%, respectively; P < .001). The incidence of grades 3 and 4 diarrhea and neutropenia was higher in the lapatinib plus paclitaxel arm. Only 4% of patients in this group reported febrile neutropenia. Cardiac events were low grade, asymptomatic, and mostly reversible. The incidence of hepatic events was similar in both arms. There were no fatal adverse events in the lapatinib plus paclitaxel arm. Conclusion This trial demonstrated that lapatinib combined with paclitaxel offers a significant and clinically meaningful survival advantage over paclitaxel alone in patients with HER2-positive MBC.

First-Line Trastuzumab Plus Epirubicin and Cyclophosphamide Therapy in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer: Cardiac Safety and Efficacy Data From the Herceptin, Cyclophosphamide, and Epirubicin (HERCULES) Trial

2010 ◽  
Vol 28 (9) ◽  
pp. 1473-1480 ◽  
Author(s):  
Michael Untch ◽  
Michael Muscholl ◽  
Sergei Tjulandin ◽  
Walter Jonat ◽  
Hans-Gerd Meerpohl ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Metastatic Breast Cancer ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
First Line ◽  
Her2 Positive ◽  
Epidermal Growth

Purpose A high incidence of congestive heart failure (CHF) has been observed in patients with metastatic breast cancer (MBC) receiving doxorubicin-based chemotherapy and trastuzumab. The Herceptin, Cyclophosphamide, and Epirubicin (HERCULES) trial evaluated trastuzumab plus cyclophosphamide and the less cardiotoxic anthracycline epirubicin. Patients and Methods This prospective trial combined a phase I dose-finding stage with a phase II randomized stage. In total, 120 patients with human epidermal growth factor receptor 2 (HER2) –positive MBC and adequate cardiac function received first-line trastuzumab (4 mg/kg intravenous loading dose, then 2 mg/kg every week) plus cyclophosphamide (600 mg/m2) and either epirubicin 60 mg/m2 (HEC-60) or 90 mg/m2 (HEC-90) for six cycles, followed by trastuzumab monotherapy until progression. Sixty patients with HER2-negative disease received epirubicin (90 mg/m2) and cyclophosphamide (EC-90) alone. The primary end point was dose-limiting cardiotoxicity (DLC). Results Incidence of DLC was 5.0%, 1.7%, and 0% in the HEC-90, HEC-60, and EC-90 arms, respectively. All DLC events were manageable. There were no cardiac-related deaths. Other adverse-event profiles were comparable across the three arms, except febrile neutropenia, which was reported in 10% of the HEC-90 arm compared with 3% of the other arms. Tumor response rates were 57%, 60%, and 25% in the HEC-60, HEC-90, and EC-90 arms, respectively; median time to progression was 12.5, 10.1, and 7.6 months, respectively. Conclusion The HEC regimen is a promising treatment option for patients with HER2-positive MBC. The lower incidence of DLC with HEC, compared with the historic incidence associated with trastuzumab plus doxorubicin, supports further evaluation of the regimen, especially in adjuvant or neoadjuvant settings.

Phase II study of lapatinib in combination with vinorelbine, as first- or second-line therapy in women with HER2-overexpressing metastatic breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 621-621
Author(s):  
Helen K. Chew ◽  
Lee Steven Schwartzberg ◽  
Suprith Badarinath ◽  
Peter Rubin ◽  
Grace Shumaker ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Metastatic Breast Cancer ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Phase Ii Study ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Second Line ◽  
Epidermal Growth

621 Background: Lapatinib (L), an inhibitor of epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2) is approved in combination with capecitabine for second-line treatment of HER2+ metastatic breast cancer (MBC). Vinorelbine (V)is a semi-synthetic vinca alkaloid approved for use in patients (pts) with MBC. A previous phase I trial provided a maximum tolerated dose of L plus V. Methods: This was a multicenter, phase II study (LPT111110; NCT00709618) to evaluate the efficacy and safety of L plus V in women with histologically confirmed stage IV HER2+ MBC, ≤1 prior chemotherapeutic regimen (no prior L or V was allowed; prior trastuzumab was permitted) and a Zubrod performance status of 0-2. Pts received L (1500 mg daily) plus V (20 mg/m2IV on Days 1, 8, 15) in a 4-week treatment cycle until disease progression or study withdrawal. Primary endpoint: overall response rate (ORR). Secondary endpoints: progression-free survival (PFS), overall survival, time to response (TTR), duration of response (DOR), time to progression, and safety assessments. Results: The study was terminated after three years due to slow enrollment; 60 pts were planned and 44 enrolled and were treated. The ORR was 41% (95% CI: 26.4%-55.4%; 4 complete responses, 14 partial responses). Investigator-assessed median (95% CI) PFS, TTR, and DOR were 24.1 (16.9-36.7), 7.5 (7.1–8.1), and 32.0 (18.0-42.3) weeks, respectively. Survival data are not available since data collection was terminated after discontinuation of study treatment. All pts experienced at least 1 adverse event (AE). Conclusions: The combination of L plus V resulted in a 41% ORR and was generally well tolerated. However, definitive conclusions could not be drawn as the study was terminated early and not powered for inference testing. Further exploration of L plus V is warranted to clearly define the role of this novel combination in the treatment of HER2+ MBC. Clinical trial information: NCT00709618. [Table: see text]

Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor–Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE

2021 ◽  
Vol 39 (1) ◽  
pp. 79-89 ◽  
Author(s):  
Stephen R. D. Johnston ◽  
Roberto Hegg ◽  
Seock-Ah Im ◽  
In Hae Park ◽  
Olga Burdaeva ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Metastatic Breast Cancer ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Clinical Benefit ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Her2 Positive ◽  
Epidermal Growth

PURPOSE Human epidermal growth factor receptor 2 (HER2) targeting plus endocrine therapy (ET) improved clinical benefit in HER2-positive, hormone receptor (HR)–positive metastatic breast cancer (MBC) versus ET alone. Dual HER2 blockade enhances clinical benefit versus single HER2 blockade. The ALTERNATIVE study evaluated the efficacy and safety of dual HER2 blockade plus aromatase inhibitor (AI) in postmenopausal women with HER2-positive/HR-positive MBC who received prior ET and prior neo(adjuvant)/first-line trastuzumab (TRAS) plus chemotherapy. This updated article reflects minor numerical corrections in some secondary efficacy analyses that resulted from programming errors and that do not change the major conclusions of the study. METHODS Patients were randomly assigned (1:1:1) to receive lapatinib (LAP) plus TRAS plus AI, TRAS plus AI, or LAP plus AI. Patients for whom chemotherapy was intended were excluded. The primary end point was progression-free survival (PFS; investigator assessed) with LAP plus TRAS plus AI versus TRAS plus AI. Secondary end points were PFS (comparison of other arms), overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR), and safety. RESULTS Three hundred fifty-five patients were included in this analysis: LAP plus TRAS plus AI (n = 120), TRAS plus AI (n = 117), and LAP plus AI (n = 118). Baseline characteristics were balanced. The study met its primary end point; superior PFS was observed with LAP plus TRAS plus AI versus TRAS plus AI (median PFS, 11 v 5.6 months; hazard ratio, 0.62 [95% CI, 0.45 to 0.88]; P = .0063). A consistent PFS benefit was observed in predefined subgroups. ORR, CBR, and OS also favored LAP plus TRAS plus AI. The median PFS with LAP plus AI versus TRAS plus AI was 8.3 versus 5.6 months (hazard ratio, 0.85 [95% CI, 0.62 to 1.17]; P = .3159). Common adverse events (AEs; ≥ 15%) with LAP plus TRAS plus AI, TRAS plus AI, and LAP plus AI were diarrhea (69%, 9%, and 51%, respectively), rash (36%, 2%, and 28%, respectively), nausea (22%, 9%, and 22%, respectively), and paronychia (30%, 0%, and 15%, respectively), mostly grade 1 or 2. Serious AEs were reported similarly across the 3 groups, and AEs leading to discontinuation were lower with LAP plus TRAS plus AI. CONCLUSION Dual HER2 blockade with LAP plus TRAS plus AI showed superior PFS benefit versus TRAS plus AI in patients with HER2-positive/HR-positive MBC. This combination offers an effective and safe chemotherapy-sparing alternative treatment regimen for this patient population.

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