Cutaneous Apocrine Adenocarcinoma of the Groin With Extramammary Paget Disease: Response to Dual HER2 Blockade With Trastuzumab and Pertuzumab

Adenocarcinoma apocrino cutáneo; Enfermedad de Paget extramamaria; TratamientoAdenocarcinoma apocri cutani; Malaltia de Paget extramamària; TractamentCutaneous apocrine adenocarcinoma; Extramammary Paget's disease; TreatmentEl carcinoma apocrino cutáneo es una neoplasia maligna rara que se asocia a mal pronóstico. La enfermedad de Paget extramamaria (EPEM) invasiva es una forma rara de adenocarcinoma que se observa principalmente en las áreas donde se encuentran las glándulas apocrinas y tiene un pronóstico peor que su estadio in situ con un riesgo mayor de neoplasias subyacentes. La diseminación epidérmica pagetoide es poco común en los carcinomas apocrinos. Se han descrito muy pocos casos que asocien estas dos entidades y se desconoce su histogénesis. Entre un 20 y un 60% de EPEM sobreexpresa HER-2/neu (c-erbB-2), con pocos casos descritos de respuesta favorable a trastuzumab (anticuerpo monoclonal recombinante contra HER-2), solo o en combinación con paclitaxel. La sobreexpresión de HER-2/neu conduce a una proliferación aumentada de las células tumorales en la EPEM, como en los cánceres de mama HER2 positivos, de comportamiento más agresivo y más recurrències

Comparison of the pharmacodynamic profiles of a biosimilar filgrastim and Amgen filgrastim: results from a randomized, phase I trial

Further to the patent expiry of Neupogen® (Amgen filgrastim), Hospira has developed a biosimilar filgrastim (Nivestim™) that may offer a clinically effective alternative for multiple hematologic and oncologic indications. Here results are reported from a phase I trial, primarily designed to compare the pharmacodynamic profiles of Hospira filgrastim and Amgen filgrastim. A phase I, single-center, double-blind, randomized trial was undertaken to demonstrate equivalence of the pharmacodynamic characteristics of Hospira filgrastim and Amgen filgrastim. Fifty healthy volunteers were randomized to receive 5 or 10 µg/kg dosing, before further randomization to treatment sequence. All volunteers received five daily subcutaneous doses of Hospira filgrastim or Neupogen, with subsequent crossover to the alternative treatment. Bioequivalence was evaluated by analysis of variance; if the estimated 90% confidence intervals (CIs) for the ratio of ‘test’ to ‘reference’ treatment means were within the conventional equivalence limits of 0.80–1.25, then bioequivalence was concluded. Forty-eight volunteers completed the study. Geometric mean absolute neutrophil count area under the curve from time 0 to the last time point at day 5 (primary endpoint) was comparable in volunteers given Hospira filgrastim or Amgen filgrastim at 5 µg/kg (ratio of means, 0.98; 90% CI, 0.92–1.05) or 10 µg/kg (ratio, 0.97; 90% CI, 0.93–1.01); 90% CIs were within the predefined range necessary to demonstrate bioequivalence. Hospira filgrastim was well tolerated with no additional safety concerns over Amgen filgrastim. Hospira filgrastim is bioequivalent with Amgen filgrastim with regard to its pharmacodynamic characteristics

Heritage: A phase III safety and efficacy trial of the proposed trastuzumab biosimilar Myl-1401O versus Herceptin

Background: Trastuzumab has revolutionized treatment of HER2+ breast cancer. Globally accessible alternatives are a critical need. We evaluated Myl-1401O, a proposed trastuzumab biosimilar, as treatment for HER2+ metastatic breast cancer (MBC), based on physicochemical analyses, nonclinical, pharmacokinetic and pharmacodynamic studies*. Methods: Heritage is a double-blind, randomized clinical trial designed to evaluate comparative efficacy and safety of Myl-1401O vs Herceptin. Eligible patients (pts) had ..

Effect of a Proposed Trastuzumab Biosimilar Compared With Trastuzumab on Overall Response Rate in Patients With ERBB2 (HER2)–Positive Metastatic Breast Cancer. A Randomized Clinical Trial

IMPORTANCE Treatment with the anti-ERBB2 humanized monoclonal antibody trastuzumab and chemotherapy significantly improves outcome in patients with ERBB2 (HER2)–positive metastatic breast cancer; a clinically effective biosimilar may help increase access to this therapy. OBJECTIVE To compare the overall response rate and assess the safety of a proposed trastuzumab biosimilar plus a taxane or trastuzumab plus a taxane in patients without prior treatment for ERBB2-positive metastatic breast cancer. DESIGN, SETTING, AND PARTICIPANTS Multicenter, double-blind, randomized, parallel-group, phase 3 equivalence study in patients with metastatic breast cancer. From December 2012 to August 2015, 500 patients were randomized 1:1 to receive a proposed biosimilar or trastuzumab plus a taxane. Chemotherapy was administered for at least 24 weeks followed by antibody alone until unacceptable toxic effects or disease progression occurred. INTERVENTIONS Proposed biosimilar (n = 230) or trastuzumab (n = 228) with a taxane. MAIN OUTCOMES AND MEASURES The primary outcome was week 24 overall response rate (ORR) defined as complete or partial response. Equivalence boundaries were 0.81 to 1.24 with a 90% CI for ORR ratio (proposed biosimilar/trastuzumab) and −15% to 15% with a 95% CI for ORR difference. Secondary outcome measures included time to tumor progression, progression-free and overall survival at week 48, and adverse events. RESULTS Among 500 women randomized, the intention-to-treat population included 458 women (mean [SD] age, 53.6 [11.11] years) and the safety population included 493 women. The ORR was 69.6% (95% CI, 63.62%-75.51%) for the proposed biosimilar vs 64.0% (95% CI, 57.81%-70.26%) for trastuzumab. The ORR ratio (1.09; 90% CI, 0.974-1.211) and ORR difference (5.53; 95% CI, −3.08 to 14.04) were within the equivalence boundaries. At week 48, there was no statistically significant difference with the proposed biosimilar vs trastuzumab for time to tumor progression (41.3% vs 43.0%; −1.7%; 95% CI, −11.1% to 6.9%), progression-free survival (44.3% vs 44.7%; −0.4%; 95% CI, −9.4% to 8.7%), or overall survival (89.1% vs 85.1%; 4.0%; 95% CI, −2.1% to 10.3%). In the proposed biosimilar and trastuzumab groups, 239 (98.6%) and 233 (94.7%) had at least 1 adverse event, the most common including neutropenia (57.5% vs 53.3%), peripheral neuropathy (23.1% vs 24.8%), and diarrhea (20.6% vs 20.7%). CONCLUSIONS AND RELEVANCE Among women with ERBB2-positive metastatic breast cancer receiving taxanes, the use of a proposed trastuzumab biosimilar compared with trastuzumab resulted in an equivalent overall response rate at 24 weeks. Further study is needed to assess safety and long-term clinical outcome. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02472964; EudraCT Identifier: 2011-001965-4

PRINCIPLES OF ; MOLECULAR ONCOLOGY

xix / 418 hlm ; 21 x 28 c

Final overall survival analysis of the phase 3 HERITAGE study demonstrates equivalence of trastuzumab-dkst to trastuzumab in HER2-positive metastatic breast cancer.

PurposeThe phase 3 HERITAGE trial demonstrated that the biosimilar trastuzumab-dkst is well tolerated with similar efficacy (measured by overall response rate [ORR] and progression-free survival [PFS]) compared with originator trastuzumab combined with taxane followed by monotherapy in patients with HER2-positive metastatic breast cancer (MBC). Herein, we present final overall survival (OS) from HERITAGE.MethodsHERITAGE is a multicenter, double-blind, randomized, parallel-group study. Patients were randomized 1:1 to receive trastuzumab-dkst or trastuzumab plus taxane followed by continued monotherapy until disease progression. Overall survival was to be assessed at 36 months or after 240 deaths, whichever occurred first, as observed from time of randomization of last patient.ResultsAt the final analysis (36 months), 242 patients in the intention-to-treat population had died during the study: 116 and 124 in the trastuzumab-dkst and trastuzumab groups, respectively, and 1 untreated patient from each treatment group. Median OS by Kaplan-Meier analysis was 35.0 months with trastuzumab-dkst and 30.2 months with trastuzumab. Evaluation of PFS showed a median of 11.1 months in both treatment groups. No new safety concerns were reported from week 48 until the end of the survival follow-up.ConclusionThis is the first phase 3 trial of a trastuzumab biosimilar to report long-term survival data similar to originator trastuzumab in patients with MBC. The comparable long-term OS between the trastuzumab-dkst and originator trastuzumab groups further supports the similarity of trastuzumab-dkst with originator trastuzumab and establishes trastuzumab-dkst as a safe and effective treatment option for patients with HER2-positive MBC. ClinicalTrials.gov NCT02472964; 6/16/2015