eBC = early breast cancer.
*EU-sourced Herceptin® was used in the LILAC study. The KANJINTI® clinical pharmacokinetic (PK) study demonstrated equivalence between EU- and US-sourced Herceptin® and KANJINTI®.
†Conducting biosimilar studies in this sensitive population provides scientific evidence supporting use in less sensitive populations.1,7
Use of trastuzumab in the neoadjuvant setting is not an approved indication in the product label for KANJINTI® or Herceptin®. The selection of the patient population was appropriate to support demonstration of no clinically meaningful differences between KANJINTI® and Herceptin®.*1,5,6
Study population: Patients with early breast cancer (eBC) in the neoadjuvant setting.
Study design: A comparative, randomized equivalence trial between KANJINTI® and Herceptin® in patients with HER2+ eBC (N = 725).
CI = confidence interval.
*EU-sourced Herceptin® was used in the LILAC study. The KANJINTI® clinical pharmacokinetic (PK) study demonstrated equivalence between EU- and US-sourced Herceptin® and KANJINTI®.
‡Central laboratory review was performed to reduce the pathologic variability at the local level.
*EU-sourced Herceptin® was used in the LILAC study. The KANJINTI® clinical pharmacokinetic (PK) study demonstrated equivalence between EU- and US-sourced Herceptin® and KANJINTI®.
‡Central laboratory review was performed to reduce the pathologic variability at the local level.
*EU-sourced Herceptin® was used in the LILAC study. The KANJINTI® clinical pharmacokinetic (PK) study demonstrated equivalence between EU- and US-sourced Herceptin® and KANJINTI®.
§Initial dose of 8 mg/kg IV then 6 mg/kg IV for remaining cycles.
**Total of up to 1 year from the first day of KANJINTI®/Herceptin® administered in the neoadjuvant phase.
††Lumpectomy or mastectomy with sentinel or axillary lymph node dissection.
adverse events OF INTEREST (EOI)1 greater than or equal to GRADE 3
Safety was assessed in both neoadjuvant and adjuvant settings to support biosimilarity. Only treatment-emergent AEs are summarized. For each category, subjects are included only once, even if they experienced multiple events in that category. Following surgery, 171 patients underwent a single transition from Herceptin® to KANJINTI® to further evaluate safety and immunogenicity.
Antidrug antibody formation was low (≤ 2%) in all study arms. No patients developed neutralizing antibodies.1
No evidence of increased cardiotoxicity for KANJINTI®—median LVEF values did not change in any study arm over the full course of the study.1
LVEF = left ventricular ejection fraction.
A randomized, single-blind, single-dose, 3-arm, parallel-group study to determine the pharmacokinetic equivalence of KANJINTI® and Herceptin® in healthy adult males. The primary objective was to evaluate bioequivalence of KANJINTI® and Herceptin® in terms of AUCinf and Cmax (equivalence criteria: 90% CI for geometric mean ratio within 0.80–1.25).2
The mean serum concentration-time profiles were similar between treatments over the entire course of sampling.2
Peak concentrations were observed approximately 1.5 to 5 hours after the start of the infusion.2
AUCinf = area under the concentration curve versus time from zero to infinity; Cmax = maximum serum concentration; PK = pharmacokinetic.
NOD/SCID mice were injected orthotopically with BT-474 human breast tumor cells that naturally overexpress HER2 receptors (8 x 106 cells per mouse). After 21 days, treatment with vehicle control, KANJINTI®, or Herceptin® was administered twice weekly by IV for 19 days. Tumor sizes were measured twice per week until day 56.
CD-1 nude mice were injected subcutaneously with NCI-N87 gastric tumor cells (5 x 106 cells per mouse). When average tumor size reached ~100 mm3, vehicle control, KANJINTI®, or Herceptin® was administered twice weekly by intraperitoneal injection for 19 days. Tumor sizes were measured three times per week until day 35.
BT-474 = metastatic human breast cancer cells; HER2 = human epidermal growth factor receptor 2; IV = intravenous; NCI-N87 = human gastric cancer cells; NOD/SCID = nonobese diabetic/severe combined immune deficient.
Analytical data can be summarized as similar with regard to: DNA sequence, monoclonal antibody protein structure, biological activity, purity, and stability.4
Boxed WARNINGS: Cardiomyopathy- Trastuzumab products administration can result in sub-clinical and clinical cardiac failure. The incidence and severity was highest in patients receiving trastuzumab with anthracycline-containing chemotherapy regimens
Evaluate left ventricular function in all patients prior to and during treatment with KANJINTI®. Discontinue KANJINTI® treatment in patients receiving adjuvant therapy and withhold KANJINTI® in patients with metastatic disease for clinically significant decrease in left ventricular function
Infusion Reactions; Pulmonary Toxicity- Trastuzumab products administration can result in serious and fatal infusion reactions and pulmonary toxicity. Symptoms usually occur during or within 24 hours of administration. Interrupt KANJINTI® infusion for dyspnea or clinically significant hypotension. Monitor patients until symptoms completely resolve. Discontinue KANJINTI® for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome
Embryo-Fetal Toxicity- Exposure to trastuzumab products during pregnancy can result in oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise patients of these risks and the need for effective contraception
Cardiomyopathy
Administration of trastuzumab products can result in sub-clinical and clinical cardiac failure. The incidence and severity was highest in patients receiving trastuzumab with anthracycline-containing chemotherapy regimens. In a pivotal adjuvant breast cancer trial, one patient who developed CHF died of cardiomyopathy
Trastuzumab products can cause left ventricular cardiac dysfunction, arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death
Trastuzumab products can also cause asymptomatic decline in left ventricular ejection fraction (LVEF)
Discontinue KANJINTI® treatment in patients receiving adjuvant breast cancer therapy and withhold KANJINTI® in patients with metastatic disease for clinically significant decrease in left ventricular function
Cardiac Monitoring
Evaluate cardiac function prior to and during treatment. For adjuvant breast cancer therapy, also evaluate cardiac function after completion of KANJINTI®
Conduct thorough cardiac assessment, including history, physical examination, and determination of LVEF by echocardiogram or MUGA scan
Monitor frequently for decreased left ventricular function during and after KANJINTI® treatment
Monitor more frequently if KANJINTI® is withheld for significant left ventricular cardiac dysfunction
Infusion Reactions
KANJINTI® administration can result in serious and fatal infusion reactions
Symptoms usually occur during or within 24 hours of KANJINTI® administration
Interrupt KANJINTI® infusion for dyspnea or clinically significant hypotension
Monitor patients until symptoms completely resolve
Discontinue KANJINTI® for infusion reactions manifesting as anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome. Strongly consider permanent discontinuation in all patients with severe infusion reactions
Infusion reactions consist of a symptom complex characterized by fever and chills, and on occasion include nausea, vomiting, pain (in some cases at tumor sites), headache, dizziness, dyspnea, hypotension, rash, and asthenia
Embryo-Fetal Toxicity
Exposure to trastuzumab products during pregnancy can result in oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise patients of these risks and the need for effective contraception
Verify the pregnancy status of females of reproductive potential prior to the initiation of KANJINTI®
Advise pregnant women and females of reproductive potential that exposure to KANJINTI® during pregnancy or within 7 months prior to conception can result in fetal harm
Advise females of reproductive potential to use effective contraception during treatment and for at least 7 months following the last dose of KANJINTI®. Advise female patients to contact their healthcare provider with a known or suspected pregnancy
Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for KANJINTI® treatment and any potential adverse effects on the breastfed child from KANJINTI® or from the underlying maternal condition
Pulmonary Toxicity
Trastuzumab products can result in serious and fatal pulmonary toxicity, which includes dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, noncardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, and pulmonary fibrosis. Such events can occur as sequelae of infusion reactions
Patients with symptomatic intrinsic lung disease or with extensive tumor involvement of the lungs, resulting in dyspnea at rest, appear to have more severe toxicity
Discontinue KANJINTI® in patients experiencing pulmonary toxicity
Exacerbation of Chemotherapy-Induced Neutropenia
In randomized, controlled clinical trials, the per-patient incidences of NCI-CTC Grade 3-4 neutropenia and of febrile neutropenia were higher in patients receiving trastuzumab in combination with myelosuppressive chemotherapy as compared to those who received chemotherapy alone. The incidence of septic death was similar among patients who received trastuzumab and those who did not
Most Common Adverse Reactions
The most common adverse reactions associated with trastuzumab products in breast cancer were fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia
The most common adverse reactions associated with trastuzumab products in metastatic gastric cancer were neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia
You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Amgen at 1-800-772-6436.
Adjuvant Breast Cancer
KANJINTI® is indicated for adjuvant treatment of HER2-overexpressing node-positive or node-negative (ER/PR-negative or with one high-risk feature*) breast cancer:
As part of a treatment regimen containing doxorubicin, cyclophosphamide and either paclitaxel or docetaxel
As part of treatment with docetaxel and carboplatin
As a single agent following multi-modality anthracycline-based therapy
Select patients for therapy based on an FDA-approved companion diagnostic for trastuzumab product.
*High-risk is defined as ER/PR positive with one of the following features: tumor size > 2 cm, age < 35 years, or tumor grade 2 or 3.
Metastatic Breast Cancer
KANJINTI® is indicated:
In combination with paclitaxel for the first line treatment of HER2-overexpressing metastatic breast cancer
As a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease
Select patients for therapy based on an FDA-approved companion diagnostic for trastuzumab product.
Metastatic Gastric Cancer
KANJINTI® is indicated, in combination with cisplatin and capecitabine or 5-fluorouracil, for the treatment of patients with HER2 overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, who have not received prior treatment for metastatic disease.
Select patients for therapy based on an FDA-approved companion diagnostic for trastuzumab product.
Herceptin® (trastuzumab) is a registered trademark of Genentech USA, Inc.
Please see full Prescribing Information, including Boxed WARNINGS.
1.von Minckwitz G, Colleoni M, Kolberg HC, et al. Efficacy and safety of ABP 980 compared with reference trastuzumab in women with HER2-positive early breast cancer (LILAC study): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2018;19:987-998.
2.Hanes V, Chow V, Zhang N, Markus R. A randomized, single-blind, single-dose study evaluating the pharmacokinetic equivalence of proposed biosimilar ABP 980 and trastuzumab in healthy male subjects. Cancer Chemother Pharmacol. 2017;79:881-888.
3.Hanes V, Born T, Chow V, et al. Functional and human pharmacokinetic similarity of ABP 980 and trastuzumab. Poster presented at: European Breast Cancer Conference; March 9-11, 2016; Amsterdam, The Netherlands.
4.US Food and Drug Administration. Guidance for industry: scientific considerations in demonstrating biosimilarity to a reference product. www.fda.gov/downloads/drugs/guidances/ucm291128.pdf. Accessed February 28, 2020.
5.KANJINTI® (trastuzumab-anns) Prescribing Information, Amgen.
6.Herceptin® (trastuzumab) Prescribing Information, Genentech, USA.
7.Cortés J, Curigliano G, Diéras V. Expert perspectives on biosimilar monoclonal antibodies in breast cancer. Breast Cancer Res Treat. 2014;144:233-239.
8.Nixon N, Hannouf M, Verna S. The evolution of biosimilars in oncology, with a focus on trastuzumab. Curr Oncol. 2018;25:S171-S179.
9.Pegram MD, Bondarenko I, Zorzetto MMC, et al. PF-05280014 (a trastuzumab biosimilar) plus paclitaxel compared with reference trastuzumab plus paclitaxel for HER2-positive metastatic breast cancer: a randomised, double-blind study. Br J Cancer. 2019;120:172-182.
10.Pivot X, Bondarenko I, Nowecki Z, et al. Phase III, randomized, double-blind study comparing the efficacy, safety, and immunogenicity of SB3 (trastuzumab biosimilar) and reference trastuzumab in patients treated with neoadjuvant therapy for human epidermal growth factor receptor 2-positive early breast cancer. J Clin Oncol. 2018;36:968-974.
11.Stebbing J, Baranau Y, Baryash V, et al. CT-P6 compared with reference trastuzumab for HER2-positive breast cancer: a randomised, double-blind, active-controlled, phase 3 equivalence trial. Lancet Oncol. 2017;18:917-928.
12.Chen X, Li C, Ewesudeo R, Yin D. Population pharmacokinetics of PF-05280014 (a trastuzumab biosimilar) and reference trastuzumab (Herceptin®) in patients with HER2-positive metastatic breast cancer. Cancer Chemother Pharmacol. 2019;84:83-92. doi:10.1007/s00280-019-03850-1 [Epub ahead of print].
13.Rugo HS, Barve A, Waller CF, et al. 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. JAMA. 2017;317:37–47.
14.Data on file, Amgen; [ABP 980 CSR 20120283; 2017].
