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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.


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Journal ArticleDOI
TL;DR: The current treatment options are discussed, a practical treatment sequencing algorithm is presented and a number of effective anti-HER2 therapies that can be used in subsequent lines of therapy to improve patient outcomes are presented.
Abstract: The advent of anti-HER2 targeted therapies has dramatically improved the outcome of HER2-positive breast cancer; however, resistance to treatment in the metastatic setting remains a challenge, highlighting the need for novel therapies. The arrival of new treatment options and clinical trials examining the efficacy of novel agents may improve outcomes in the metastatic setting, including in patients with brain metastases. In the first-line setting, we can potentially cure a selected number of patients treated with pertuzumab + trastuzumab + taxane. In the second-line setting, clinical trials show that trastuzumab deruxtecan (T-DXd) is a highly effective option, resulting in a shift from trastuzumab emtansine (T-DM1) as the previous standard of care. Moreover, we now have data for patients with brain metastases to show that tucatinib + trastuzumab + capecitabine can improve survival in this higher-risk group and be an effective regimen for all patients in the third-line setting. Finally, we have a number of effective anti-HER2 therapies that can be used in subsequent lines of therapy to improve patient outcomes. This review paper discusses the current treatment options and presents a practical treatment sequencing algorithm in the context of the Canadian landscape.

4 citations

Journal ArticleDOI
Uwe Schirmer1
28 Dec 2022-Cancers
TL;DR: The TRIUMPH study as discussed by the authors showed promising efficacy for patients with HER2-positive mCRC confirmed by tissue-and/or blood-based techniques, which led to the regulatory approval of this combination therapy in Japan.
Abstract: Human epidermal growth factor receptor 2 (HER2) amplification has emerged as a biomarker in colorectal cancer (CRC), occurring in 1-4% of metastatic CRC (mCRC). In addition to conventional methods, such as immunohistochemistry and fluorescence in situ hybridization, next-generation sequencing-based tissue or circulating tumor DNA analysis has recently been used to identify HER2 amplification and assess HER2 overexpression. Prospective clinical trials have demonstrated the efficacy of HER2-targeted therapies in HER2-positive mCRC. The TRIUMPH study, a phase II study of dual HER2 antibodies, i.e., pertuzumab plus trastuzumab, demonstrated promising efficacy for patients with HER2-positive mCRC confirmed by tissue-and/or blood-based techniques, which led to the regulatory approval of this combination therapy in Japan. The mechanisms associated with efficacy and resistance have also been explored in translational studies that incorporate liquid biopsy in prospective trials. In particular, HER2 copy number and co-alterations have repeatedly been reported as biomarkers related to efficacy. To improve the therapeutic efficacy of the current strategy, many clinical trials with various HER2-targeted agents are ongoing. This review discusses the molecular basis of HER2-targeted therapeutic strategies for patients with HER2-positive mCRC.

4 citations

Journal ArticleDOI
15 Oct 2013-Drugs
TL;DR: Evidence-based guidance for sequencing anti- HER2 therapy throughout the continuum of breast cancer therapy is provided to optimally choose, utilize, and sequence anti-HER2 therapy in early as well as metastatic breast cancer.
Abstract: With the advent of the monoclonal antibody trastuzumab over 2 decades ago for breast cancer therapy, the outcome of patients with human epidermal growth factor receptor (HER) 2-positive disease has improved dramatically. Based on its substantial efficacy and good tolerability, trastuzumab has become the therapeutic gold standard for early as well as advanced breast cancer. Nevertheless, despite adjuvant trastuzumab, patients do experience recurrence and require further anti-HER2-targeted therapy. Next to the small molecule tyrosine kinase inhibitor lapatinib, which was the first approved therapy option after trastuzumab failure, several new anti-HER2 agents are currently already available for clinical use [i.e. pertuzumab, T-DM1 (trastuzumab emtansine)] or are still being evaluated (e.g. afatinib, neratinib). Recent evidence from neoadjuvant as well as metastatic therapy suggests that dual blockade may be superior to single-agent HER2 blockade. While the number of available or potential therapies has increased considerably, no additional predictive biomarkers beyond HER2 have been validated for the use of the different anti-HER2 therapies. Moreover, novel therapeutic concepts such as the antibody-drug conjugate T-DM1 warrant excellent determination methodology for HER2 and suggest re-evaluation of tumor biology upon first metastasis. The clinical challenge remains to optimally choose, utilize, and sequence anti-HER2 therapy in early as well as metastatic breast cancer. This article will provide evidence-based guidance for sequencing anti-HER2 therapy throughout the continuum of breast cancer therapy.

4 citations

Journal ArticleDOI
TL;DR: In this article, pertuzumab exposure-response (ER) analysis was conducted using logistic regression, where the authors derived individual pertuzumaab exposures in the PH FDC SC arm.
Abstract: To characterize pertuzumab pharmacokinetics (PK) in FeDeriCa (NCT03493854: fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection [PH FDC SC] versus intravenous pertuzumab plus trastuzumab); derive individual pertuzumab exposures in the PH FDC SC arm for subsequent pertuzumab exposure–response (ER) analyses; compare observed trastuzumab PK with predicted exposures from a previous SC trastuzumab model; assess whether pertuzumab affects trastuzumab PK; evaluate pertuzumab exposure–efficacy and –safety relationships and support the approved SC dosing regimen. Population pharmacokinetic modeling and simulations were used to describe the data. Standard goodness-of-fit diagnostics and prediction-corrected visual predictive checks were used for model performance assessment. Covariates were included from previously reported models. ER analysis was conducted using logistic regression. SC pertuzumab PK was described adequately by a two-compartment model with first-order absorption; significant covariates included in the final model were albumin, lean body weight, and Asian region; however, these appeared not to be clinically relevant. Trastuzumab concentrations were described adequately by the previous model; there was no evidence of a pertuzumab effect on trastuzumab PK as part of PH FDC SC and higher model-predicted pertuzumab exposure was not associated with differences in pathologic complete response rate or an increased probability of selected grade ≥ 3 adverse events of interest. The approved PH FDC SC dose [loading: 1200/600 mg pertuzumab/trastuzumab (15 mL); maintenance: 600 mg pertuzumab/trastuzumab (10 mL) and 2000 U/mL recombinant human hyaluronidase every 3 weeks] provides a positive benefit–risk profile with comparable efficacy and safety to intravenous pertuzumab plus trastuzumab.

4 citations

Journal ArticleDOI
TL;DR: A case of HER2-positive MC with an unusual signet ring cell differentiation showing pathologic complete response (pCR) after neoadjuvant chemotherapy with trastuzumab and pertuzumAB is presented.
Abstract: Mucinous carcinoma (MC) is a rare subtype of breast cancer, which is composed of tumor cells floating in the abundant extracellular mucin. This form of cancer is usually estrogen receptor/progesterone receptor positive and human epidermal growth factor receptor 2 (HER2) negative. Here, we present a case of HER2-positive MC with an unusual signet ring cell differentiation. It is very rare that a breast tumor consists entirely of signet ring cells. The tumor showed pathologic complete response (pCR) after neoadjuvant chemotherapy with trastuzumab and pertuzumab. pCR of HER2-positive MC has rarely been described in literature. It is important to consider the biological heterogeneity of MCs for effective management.

4 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
2023372
2022307
2021158
2020144
2019143
2018130