OGIVRI™ LYOPHILIZED POWDER FOR INJECTION 440MG PER VIAL [SIN15850P]

Product Info

OGIVRI™ LYOPHILIZED POWDER FOR INJECTION 440MG PER VIAL

[SIN15850P]

Therapeutic indications

Adjuvant therapy in Early Breast Cancer

Ogivri™ is indicated for the treatment of adult patients with HER2 positive early breast cancer (EBC).

• Following surgery, chemotherapy (neoadjuvant or adjuvant) and radiotherapy (if applicable) (see section "Pharmacodynamic properties" – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

• Following adjuvant chemotherapy with doxorubicin and cyclophosphamide, in combination with paclitaxel or docetaxel.

• In combination with adjuvant chemotherapy consisting of docetaxel and carboplatin.

• In combination with neoadjuvant chemotherapy followed by adjuvant Ogivri™ therapy, for locally advanced (including inflammatory) disease or tumours > 2 cm in diameter (see section "Warnings and Precautions" and "Pharmacodynamic properties" – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Ogivri™ should only be used in patients with metastatic or EBC whose tumours have either HER2 overexpression or HER2 gene amplification as determined by an accurate and validated assay.

Metastatic Breast Cancer

Ogivri™ is indicated for the treatment of adult patients with HER2 positive metastatic breast cancer (MBC):

• As monotherapy for the treatment of those patients who have received at least one chemotherapy regimen for their metastatic disease.

• In combination with paclitaxel for the treatment of those patients who have not received chemotherapy for their metastatic disease.

• In combination with an aromatase inhibitor for the treatment of postmenopausal patients with hormone-receptor positive MBC, not previously treated with trastuzumab.

This indication is based on data from one Phase III trial which studied the use of Herceptin in combination with anastrozole (see Clinical Studies – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Experience with other aromatase inhibitors is limited.

Metastatic Gastric Cancer

Ogivri in combination with capecitabine or 5-fluorouracil and cisplatin is indicated for the treatment of adult patients with HER2 positive metastatic adenocarcinoma of the stomach or gastroesophageal junction who have not received prior anticancer treatment for their metastatic disease.

Ogivri should only be used in patients with metastatic gastric cancer (MGC) whose tumours have HER2 overexpression as defined by IHC2+ and a confirmatory FISH result, or by an IHC 3+ result. Accurate and validated assay methods should be used (see section "Warnings and Precautions" and "Pharmacodynamic properties" – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Posology and Method of Administration

Patient Selection

Select patients based on HER2 protein overexpression or HER2 gene amplification in tumor specimens [see Indications and Usage and Clinical Studies – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information]. Assessment of HER2 protein overexpression and HER2 gene amplification should be performed using tests specific for breast or gastric cancers by laboratories with demonstrated proficiency.

Assessment of HER2 protein overexpression and HER2 gene amplification in metastatic gastric cancer should be performed using tests specifically for gastric cancers due to differences in gastric vs. breast histopathology, including incomplete membrane staining and more frequent heterogeneous expression of HER2 seen in gastric cancers.

Improper assay performance, including use of suboptimally fixed tissue, failure to utilize specified reagents, deviation from specific assay instructions, and failure to include appropriate controls for assay validation, can lead to unreliable results.

Recommended Doses and Schedules

• Do not administer as an intravenous push or bolus. Do not mix Ogivri™ with other drugs.

• Do not substitute Ogivri™ (trastuzumab) for or with trastuzumab emtansine.

Adjuvant Treatment, Early Breast Cancer

Three-weekly and weekly schedule

As a three-weekly regimen the recommended initial loading dose of trastuzumab is 8 mg/kg body weight. The recommended maintenance dose of trastuzumab at three-weekly intervals is 6 mg/kg body weight, beginning three weeks after the loading dose.

As a weekly regimen (initial loading dose of 4 mg/kg followed by 2 mg/kg every week) concomitantly with paclitaxel following chemotherapy with doxorubicin and cyclophosphamide.

Metastatic Treatment, Breast Cancer:

Three-weekly schedule

The recommended initial loading dose is 8 mg/kg body weight. The recommended maintenance dose at three-weekly intervals is 6 mg/kg body weight, beginning three weeks after the loading dose.

Weekly schedule

The recommended initial loading dose of trastuzumab is 4 mg/kg body weight administered as a 90-minute intravenous infusion. Patients should be observed for fever and chills or other infusion-associated symptoms (see Undesirable effects – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Interruption of the infusion may help control such symptoms. The infusion may be resumed when symptoms abate.

The recommended weekly maintenance dose of trastuzumab is 2 mg/kg body weight, beginning one week after the loading dose. If the prior dose was well tolerated, the dose can be administered as a 30-minute infusion. Patients should be observed for fever and chills or other infusion-associated symptoms (see Undesirable effects – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Administration in combination with paclitaxel.

As per published literature, paclitaxel was administered the day following the first dose of trastuzumab and immediately after the subsequent doses of trastuzumab if the preceding dose of trastuzumab was well tolerated.

Administration in combination with an aromatase inhibitor.

As per published literature, in the pivotal trial trastuzumab and anastrozole were administered from day 1. There were no restrictions on the relative timing of trastuzumab and anastrozole at administration.

Metastatic Gastric Cancer:

Three-weekly schedule

The recommended initial loading dose is 8 mg/kg body weight. The recommended maintenance dose at three-weekly intervals is 6 mg/kg body weight, beginning three weeks after the loading dose.

Important Dosing Considerations

If the patient has missed a dose of Ogivri® by one week or less, then the usual maintenance dose (weekly schedule: 2 mg/kg; three-weekly schedule: 6 mg/kg) should be administered as soon as possible. Do not wait until the next planned cycle. Subsequent Ogivri® maintenance doses should be administered 7 days or 21 days later according to the weekly or three-weekly schedules, respectively.

If the patient has missed a dose of Ogivri® by more than one week, a re-loading dose of Ogivri® should be administered over approximately 90 minutes (weekly schedule: 4 mg/kg; three-weekly schedule: 8 mg/kg) as soon as possible. Subsequent Ogivri® maintenance doses (weekly schedule: 2 mg/kg; three-weekly schedule 6 mg/kg) should be administered 7 days or 21 days later according to the weekly or three-weekly schedules, respectively.

Infusion Reactions

[see Boxed Warning, Warnings and Precautions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information]

• Decrease the rate of infusion for mild or moderate infusion reactions

• Interrupt the infusion in patients with dyspnea or clinically significant hypotension

• Discontinue Ogivri® for severe or life-threatening infusion reactions.

Cardiomyopathy

[see Boxed Warning, Warnings and Precautions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information]

Assess left ventricular ejection fraction (LVEF) prior to initiation of Ogivri® and at regular intervals during treatment. Withhold Ogivri® dosing for at least 4 weeks for either of the following:

• ≥16% absolute decrease in LVEF from pre-treatment values

• LVEF below institutional limits of normal and ≥10% absolute decrease in LVEF from pretreatment values.

Ogivri® may be resumed if, within 4 to 8 weeks, the LVEF returns to normal limits and the absolute decrease from baseline is ≤15%.

Permanently discontinue Ogivri™ for a persistent (>8 weeks) LVEF decline or for suspension of Ogivri® dosing on more than 3 occasions for cardiomyopathy.

Contraindications

Patients with known hypersensitivity to trastuzumab, murine proteins, hyaluronidase or to any other component of the product. Patients with severe dyspnoea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.