Pertuzumab

About: Pertuzumab is a research topic. Over the lifetime, 1453 publications have been published within this topic receiving 73219 citations. The topic is also known as: 2C4 Antibody & MOAB 2C4.

Open label, randomized, phase II study of pertuzumab (P) in patients (pts) with metastatic breast cancer (MBC) with low expression of HER2

Abstract: 3068 Background: P is the 1st of a new class of targeted therapeutics known as HER-dimerization inhibitors (HDI). It blocks ligand-associated heterodimerization of HER2 with other HER kinase family members, thereby inhibiting intracellular signaling. Preclinical activity of P in breast cancer has been shown to be independent of the HER2 expression level. In this study the primary endpoint was response rate according to RECIST. Secondary endpoints were: rate of stable disease (SD), toxicity profile, pharmacokinetics (PK). Methods: 79 pts in total were randomized to receive P every 3 weeks as an IV infusion either at 420 mg with a loading dose of 840 mg (arm A) or at 1050 mg (arm B). Selection criteria were: progressing MBC with low HER2 expression, anthracycline pretreatment, ≤ 2 chemotherapy regimens for MBC and LVEF ≥ 50%. Results: Out of 79 recruited pts, 78 were included in the intent to treat population. In arm A 2 partial responses (PR) and 18 SD were observed in 41 pts. In arm B 14 SD were observed ...

Tumor therapy with a combination of anti-her2 antibodies

Abstract: Method of treating a patient suffering from HER2 positive cancer, which does not respond to a monotherapy with the anti-HER2 antibodies trastuzumab or pertuzumab, with a combination of trastuzumab and pertuzumab. Articles of manufacture comprising both trastuzumab and pertuzumab.

Trastuzumab-induced cardiotoxicity: a review of clinical risk factors, pharmacologic prevention, and cardiotoxicity of other HER2-directed therapies

Abstract: Despite great success as a targeted breast cancer therapy, trastuzumab use may be complicated by heart failure and loss of left ventricular contractile function. This review summarizes the risk factors, imaging, and prevention of cardiotoxicity associated with trastuzumab and other HER2-targeted therapies. Cardiovascular disease risk factors, advanced age, and previous anthracycline treatment predispose to trastuzumab-induced cardiotoxicity (TIC), with anthracycline exposure being the most significant risk factor. Cardiac biomarkers such as troponins and pro-BNP and imaging assessments such as echocardiogram before and during trastuzumab therapy may help in early identification of TIC. Initiation of beta-adrenergic antagonists and angiotensin converting enzyme inhibitors may prevent TIC. Cardiotoxicity rates of other HER2-targeted treatments, such as pertuzumab, T-DM1, lapatinib, neratinib, tucatinib, trastuzumab deruxtecan, and margetuximab, appear to be significantly lower as reported in the pivotal trials which led to their approval. Risk assessment for TIC should include cardiac imaging assessment and should incorporate prior anthracycline use, the strongest risk factor for TIC. Screening and prediction of cardiotoxicity, referral to a cardio-oncology specialist, and initiation of effective prophylactic therapy may all improve prognosis in patients receiving HER2-directed therapy. Beta blockers and ACE inhibitors appear to mitigate risk of TIC. Anthracycline-free regimens have been proven to be efficacious in early HER2-positive breast cancer and should now be considered the standard of care for early HER2-positive breast cancer. Newer HER2-directed therapies appear to have significantly lower cardiotoxicity compared to trastuzumab, but trials are needed in patients who have experienced TIC and patients with pre-existing cardiac dysfunction.

Pertuzumab in the treatment of HER2-positive breast cancer: an evidence-based review of its safety, efficacy, and place in therapy

Abstract: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is a distinct subset of breast cancer that results from overexpression of HER2 protein. Pertuzumab-a recombinant humanized monoclonal antibody that binds to the extracellular dimerization domain II of HER2-was recently approved for adjuvant therapy and neoadjuvant therapy of HER2-positive early breast cancer. As pertuzumab and trastuzumab bind to different domains of the extracellular dimerization domain of HER2, a combination therapy of pertuzumab and trastuzumab is beneficial for the treatment of metastatic cancer, advanced local cancer, or early cancer by dual HER2 blockage. Many clinical trials have been performed using pertuzumab for breast cancer patients; these include the CLEOPATRA trial for palliative therapy, the APHINITY trial for adjuvant therapy, and the NeoSphere and the TRYPHAENA trials for neoadjuvant therapy. These trials revealed pertuzumab to be a safe and effective drug regardless of the patient age and hormone receptor status. Notably, pertuzumab use was associated with severe cardiac toxicity in some cases; however, the risk of pertuzumab-induced cardiac dysfunction was low. The most common adverse effect associated with pertuzumab-use was diarrhea, but most cases were not severe. Several different chemotherapeutic agents have been investigated to determine optimal chemotherapeutic combinations for dual HER2 blockage. Some exploratory analyses indicate that pertuzumab treatment offered little benefit to patients with node-negative and small primary tumors; pertuzumab treatment was also found not be cost-effective. Further research will reveal the appropriate usage of pertuzumab for treating a subset of eligible patients.

A Phase I Study of the Safety and Pharmacokinetics of the Combination of Pertuzumab (rhuMab 2C4) and Capecitabine in Patients with Advanced Solid Tumors

Abstract: Purpose: To study the safety, pharmacokinetics, and recommended dose of the combination of pertuzumab, a humanized monoclonal antibody HER2-dimerization inhibitor, and capecitabine in patients with advanced malignancies. Experimental Design: Patients that had progressed to standard treatment were treated with pertuzumab at a fixed dose of 1,050 mg given i.v. on day 1 plus capecitabine at doses of 825-1,000-1,250 mg/m 2 , twice daily orally on days 1 to 14 of each 21-day treatment cycle, in three sequential cohorts. The pharmacokinetics of capecitabine and pertuzumab were studied. Patients received a single dose of capecitabine in a pretreatment phase (day −7) followed by serum sampling for capecitabine and its metabolites. Results: Nineteen patients were accrued and 18 were assessable. The combination of capecitabine and pertuzumab was well tolerated at all dose levels and no dose-limiting toxicities were observed. The most frequent adverse event was asthenia, which was grade 3 in two patients. One asymptomatic pulmonary embolism occurred. No other grade 3 or 4 adverse events or cardiac or left ventricular ejection fraction events were reported. There was no apparent change in the pharmacokinetics of capecitabine and its metabolites when combined with pertuzumab. The pharmacokinetics of pertuzumab was apparently not modified when administered with capecitabine. Disease stabilization was observed in 11 patients. Conclusions: Pertuzumab and capecitabine were well tolerated at all dose levels. Escalation beyond the highest dose level tested was not planned, as this included the recommended doses of monotherapy for both drugs. In conclusion, this combination is ready for phase II testing.