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.

Technology evaluation: pertuzumab, Roche/Genentech/Chugai.

Abstract: Genentech, Roche and Chugai are developing pertuzumab, a next-generation trastuzumab-like molecule (an anti-HER/neu monoclonal antibody), for the potential treatment of cancer. Pertuzumab is currently undergoing phase II clinical trials.

Abstract S6-03: The prognosis of small HER2+ breast cancers: A meta-analysis of the randomized trastuzumab trials

Abstract: Background Trastuzumab (T) combined with chemotherapy improves survival of women with HER2-positive breast cancer. Dual therapy with T and other HER-2 targeted agents (lapatinib/pertuzumab) has demonstrated improved efficacy compared to T alone in advanced breast cancer, and is in clinical trials in early stage disease. We hypothesize that subgroups of patients with HER2-positive tumors and limited tumor burden (tumor size and no or few positive lymph nodes) have a favorable outcome and would not be candidates for dual therapy. This study will analyze the disease-free survival (DFS)and overall survival (OS) of patients with early stage breast cancer treated with chemotherapy and T in the seminal randomized studies (RCTs). Methods RCTs were identified by a Medline search from 2004-2013. Trial groups from five phase III RCTs agreed to provide data. View this table: The ER+/HER2+ and the ER-/HER2+ cohorts will be analyzed separately. Patients with tumors 3 cm or smaller (T1a, T1b, T1c and >2 cm- 3cm) and 0, 1, 2 and 3 positive lymph nodes will be included. Initially a log rank test will be used to determine if the survival results are different by study. If there is no difference across studies, Kaplan-Meier survival curves with confidence intervals will be estimated. If there is a difference between studies, individual Kaplan-Meier curves will be estimated and the mean of the curves will be estimated along with confidence intervals using the adjusted standard deviation. Estimates at 3, 5 and 8 years will be presented as well as estimates of the event rates within each subpopulation defined by tumor size, number of positive lymph nodes, and ER status. Survival endpoints of DFS, and OS as defined in the original studies will be analyzed. Results and Conclusion Data from the five trials will be analyzed and an abstract provided prior to the meeting. Subgroups of patients with a very favorable outcome when treated with adjuvant chemotherapy and T will be identified. Our survival estimates might serve as benchmarks for future trials evaluating therapy reduction. Our results will complement those of the Dana Farber single arm multicenter trial in patients with “low risk” HER2-positive disease (APT trial; [NCT00542451][1]), being submitted to SABCS 2013. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S6-03. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00542451&atom=%2Fcanres%2F73%2F24_Supplement%2FS6-03.atom

Pooled Analysis of Cardiac Safety in Patients Treated with Pertuzumab.

Abstract: Background: Pertuzumab, a monoclonal antibody, is a human epidermal growth factor receptor 2 (HER2)-dimerisation inhibitor directed to the dimerisation epitope of HER2, with promising activity when given with trastuzumab to patients with HER2-positive metastatic breast cancer following progression on trastuzumab. 1 As anti-HER2 treatment has been associated with cardiac dysfunction, we investigated the incidence of reduced left ventricular ejection fraction (LVEF) and congestive heart failure (CHF) in patients treated with pertuzumab as single agent or in combination with cytotoxic or anti-HER therapy. Methods: We analysed patients in completed Phase II studies with pertuzumab. Cardiac dysfunction was defined as: 1) reduced LVEF (baseline normal: LVEF reduced ≥10% absolute and to below 50%); 2) symptomatic CHF: any symptoms suggestive of CHF counted (severity then classified according to New York Heart Association). Results: In 554 patients analysed, the overall incidence of reduced LVEF was 5.8% and of CHF 0.7%. Individual data for patients in different treatment protocols are shown in Table 1.The majority of patients with reduced LVEF or symptomatic CHF had significant improvement or return to baseline function on follow-up or with standard cardiac medication. Conclusions: Overall, the incidence of cardiac dysfunction in Phase II studies of patients treated with pertuzumab was low. When combined with trastuzumab in selected patients, there is no apparent indication that pertuzumab exacerbates the known risk of reduced LVEF and CHF with trastuzumab. 2 These data suggest that the combination of pertuzumab with trastuzumab or chemotherapy for HER2-positive breast cancer appears safe from a cardiac perspective with appropriate monitoring in ongoing studies. References 1. Gelmon K et al. Poster 1026 presented at the 44th ASCO Annual Meeting, Chicago, Illinois, USA, 30 May-3 June, 20082. Muehlbauer S et al. Abstract presented at SABCS 2008; abs 6136 Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5088.

Abstract P4-14-12: Interim results from the first open-label, multicenter, phase IIIb study investigating the combination of pertuzumab with subcutaneous trastuzumab and a taxane in patients with HER2-positive metastatic breast cancer (SAPPHIRE)

Abstract: Background: Intravenous (IV) trastuzumab has proven clinical benefits in patients (pts) with human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). The use of pertuzumab, which targets HER2 through an independent epitope to that of trastuzumab, in combination with IV trastuzumab and docetaxel has shown improved efficacy with acceptable toxicity in metastatic (m) BC. Subcutaneous (SC) and IV trastuzumab formulations have shown comparable efficacy. This study aimed to assess the safety, tolerability, and efficacy of combining IV pertuzumab with SC trastuzumab and a taxane, as 1st-line therapy in pts with HER2+ mBC, a combination for which results have not previously been reported. Here we present demographics and interim safety data. Methods: This is an open-label, multicentre, phase IIIb study. The primary objective was the safety and tolerability of IV pertuzumab with SC trastuzumab and investigator9s choice of taxane. Pts aged ≥18 years with confirmed HER2-positive [IHC3+ or ISH+] mBC with at least one measurable lesion and/or non-measurable disease according to RECIST version 1.1 and ECOG performance status (PS) 0-2 were included. Pts received IV pertuzumab every 3 weeks (loading dose=840 mg; subsequent doses=420mg) combined with SC trastuzumab at 600mg/5mL every 3 weeks and the investigator9s choice of taxane (docetaxel, paclitaxel, or nab-paclitaxel). Treatment continued until disease progression, unacceptable toxicity, or consent was withdrawn, whichever occurred first. The incidence and severity of adverse events (AEs), serious (S) AEs and AEs leading to premature discontinuation of study treatment were analyzed. Results: The planned 50 pts have been recruited from 12 centres; mean age 53 (SD-12.0) years; the majority white (84%), ECOG PS 0 (n=33) and PS 1 (n=15). 98% were females; 61% post-menopausal. Taxanes of choice were nab-paclitaxel (n=36), docetaxel (n=13) and paclitaxel (n=1). Any grade AEs (n=627) were reported in 100% pts; majority grade 1-2, the most common being diarrhoea, fatigue, peripheral neuropathy, alopecia, nausea, rash, headache and vomiting. Grade 3+ AEs (n=54) were reported in 52% pts, most commonly neutropenia (10%), febrile neutropenia (8%) and diarrhoea (6%). SAEs (n=36) were reported in 48% pts; most commonly pyrexia (14%), febrile neutropenia (8%), neutropenia (4%), pulmonary embolism (4%) and cellulitis (4%). Five AEs of suspected cardiac disorders were reported in 4 pts (atrial fibrillation, cardiomyopathy, myocardial ischemia, palpitations and ejection fraction decreased). AEs leading to study drug discontinuation (n=3) were reported in 3 pts (LVEF decreased, syncope and blister). AEs leading to chemotherapy discontinuation (n=14) were reported in 20% pts. Conclusion: We report the first data on the use of pertuzumab with SC trastuzumab. The observed safety profile is consistent with that previously reported in the CLEOPATRA (Baselga, et al. NEJM 2012;366:109-19), PERUSE [Bachelot, et al. JCO 2014;32:5s(abstr#548)] and HannaH (Ismael, et al. Lancet Oncol 2012;13:869-78) studies, with no unexpected safety signals. Clinical trial information:NCT02019277. Citation Format: Woodward N, De Boer RH, Redfern A, White M, Young J, Truman M, Beith J. Interim results from the first open-label, multicenter, phase IIIb study investigating the combination of pertuzumab with subcutaneous trastuzumab and a taxane in patients with HER2-positive metastatic breast cancer (SAPPHIRE). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-14-12.

Trends and Novel Approaches in Neoadjuvant Treatment of Breast Cancer.

Abstract: Breast cancer is the most prevalent malignant disease in women worldwide. Traditionally, surgical tumour resection was the primary step within the treatment algorithm of early stage disease; systemic therapy in order to reduce the rate of systemic recurrences followed. National Surgical Adjuvant Breast and Bowel Project (NSABP) trial B-18 found that pre- and postoperative administration of chemotherapy was equally effective. This study therefore established neoadjuvant chemotherapy as a valid treatment option, as the breast conservation rate is increased. Modern neoadjuvant regimens encompassing anthracyclines and taxanes yield pathological complete response (pCR) rates of around 20%, with higher efficacy observed in triple-negative tumours. The antibody trastuzumab is the first targeted agent established in neoadjuvant regimens for the treatment of Her2-positive breast cancer, as it raised pCR rates up to 50%. Novel approaches are aiming to increase the efficacy of neoadjuvant therapy. Inclusion of capecitabine might further increase pCR rates in selected patients, although data are not unanimous throughout the respective clinical trials. In patients harbouring BRCA-1 germline mutations, platinum derivatives are apparently promising. Novel Her2-targeted agents such as lapatinib and pertuzumab are currently under investigation in several clinical trials, while the role of bevacizumab, a monoclonal antibody inhibiting angiogenesis, awaits future clarification.