What s New With HER2?

Transcription

1 What s New With HER2? Trastuzumab emtansine and pertuzumab for metastatic breast cancer Lindsay Livingston Pharmacist CancerCare Manitoba October 3, 2014

2 Presenter Disclosure Faculty: Lindsay Livingston Relationships with commercial interests: none to declare

3 Mitigating Potential Bias Not applicable

4 Learning Objectives Describe the indication for use of both medications Explain administration considerations for both medications, including duration of infusions and post-infusion observation requirements List three potential adverse effects of each medication

5 Targeted Therapy Medications used to identify and attack specific molecules located on the surface of, or inside, cancer cells. Target cancer cells with less harm to normal cells

6 HER2 as a Target HER2 = human epidermal growth factor receptor 2 HER2 activation triggers signaling pathways cell growth, proliferation and survival HER2 overexpressed in ~25% of breast cancers More aggressive disease, poorer prognosis

7 Pertuzumab: Mechanism of Action Humanized monoclonal antibody Binds to HER2 (different site than trastuzumab) HER2 dimerization inhibitor stops intracellular signaling arrests cell growth and causes cell death Complementary action with trastuzumab

8 Pertuzumab: Indication First-line treatment of metastatic HER2+ breast cancer in combination with trastuzumab and docetaxel. (FDA approved second indication: neoadjuvant treatment)

9 Pertuzumab: Dosing and Administration Every 3 weeks 840 mg loading dose infused over 60 minutes, with 60 minute observation 420 mg doses subsequently, over minutes, with 30 minute observation Order of administration: pertuzumab trastuzumab docetaxel Cycle #1: pertuzumab on day 1, then trastuzumab + docetaxel on day 2

10 Pertuzumab: Precautions Cardiotoxicity LVEF monitoring Immune reactions Infusion-related (13-19% incidence) Hypersensitivity (11%, severe: 2-5%) majority of reactions mild-moderate and resolve with appropriate treatment anaphylaxis (1%)

11 Pertuzumab: Adverse Effects In combination with trastuzumab and docetaxel, most common (> 30%): diarrhea alopecia neutropenia nausea fatigue rash peripheral neuropathy

12 Trastuzumab Emtansine: Mechanism of Action Antibody-drug conjugate trastuzumab linked to DM1 (microtubule inhibitor) delivers chemotherapy directly to cells overexpressing HER2

13 Trastuzumab Emtansine: Indication Treatment of HER2+ metastatic breast cancer in patients who have received prior treatment with both trastuzumab and a taxane (separately, or in combination). CCMB formulary: disease progression despite prior treatment with trastuzumab in the metastatic setting OR relapse/progression within 6 months of completion of adjuvant trastuzumab.

14 Trastuzumab Emtansine: Dosing and Administration Every 3 weeks 3.6 mg/kg Dose reductions for hepatotoxicity and thrombocytopenia First dose infused over 90 minutes, with > 90 minute observation Subsequent doses over 30 minutes (if first dose well-tolerated), and > 30 minute observation

15 Trastuzumab Emtansine: Precautions Cardiotoxicity LVEF monitoring Hepatotoxicity Thrombocytopenia Immune reactions Infusion-related reactions Hypersensitivity Pulmonary toxicity

16 Trastuzumab Emtansine: Adverse Effects Thrombocytopenia, anemia, neutropenia Bleeding Peripheral neuropathy (22%) transaminases, bilirubin, hypokalemia Muscle/joint pain Rash Mouth sores Constipation, diarrhea

17 Take Home Message HER2 continues to be important target Regular cardiac monitoring is important for pertuzumab and trastuzumab emtansine Watch for decreases in LVEF; product monographs suggest course of action Observation period for infusion-related and hypersensitivity reactions Monitor bloodwork closely for trastuzumab emtansine (platelets, transaminases, etc.)

18 References CancerCare Manitoba Provincial Oncology Drug Formulary, July 2014 FDA Approves Pertuzumab for Neoadjuvant Breast Cancer October 1, 2013 (asco.org/advocacy/fda-approves-pertuzumab-breast-cancer) Herceptin (trastuzumab) product monograph, Hoffmann-La Roche Limited, accessed using Health Canada Drug Product Database Kadcyla TM (trastuzumab emtansine) product monograph, Hoffmann-La Roche Limited, accessed using Health Canada Drug Product Database Perjeta.com website Perjeta (pertuzumab) product monograph, Hoffmann-La Roche Limited, accessed using Health Canada Drug Product Database Pertuzumab health professional monograph, BC Cancer Agency Drug Manual, January 1, 2014 Trastuzumab emtansine health professional monograph, BC Cancer Agency Drug Manual, May 1, 2014