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.

Abstract OT1-03-03: Phase II, open label, randomized, biomarker study of immune-mediated mechanism of action of neoadjuvant subcutaneous trastuzumab in patients with operable or locally advanced/Inflammatory HER2-positive breast cancer. ImmunHER trial on behalf of the Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC)

Abstract: Background: Tumor-infiltrating lymphocytes (TILs) have been reported to be associated with increased therapeutic efficacy of trastuzumab/pertuzumab-based neoadjuvant therapy (NT) in patients (pts) with HER2-positive breast cancer (BC). Subcutaneous (SC) trastuzumab has non-inferior efficacy to intravenous (IV) administration, with a similar safety profile. Interestingly, SC trastuzumab has been observed to be more immunogenic than IV trastuzumab and act at different immunologic levels. Therefore, by modifying the modality of administration of trastuzumab, it could be possible to interfere with different immune pathways and exert a favorable immunomodulation in HER2-positive BC. Methods: In this non-comparative, phase II, neoadjuvant, randomized study, pts were eligible if they had previously untreated, histologically confirmed, locally advanced, inflammatory, or early-stage HER2-positive BC. Pts were treated with FEC (fluorouracil 500 mg/m2; epirubicin 75 mg/m2; cyclophosphamide 500 mg/m2) q21 × 3 cycles. Then, they were randomly assigned (1:1) to receive: docetaxel (75 mg/m2) plus pertuzumab (840 mg loading dose (LD), then 420 mg) plus IV trastuzumab (8 mg/kg LD, then 6 mg/kg) q21 × 4 cycles (arm A) or, docetaxel plus pertuzumab plus SC trastuzumab (fixed dose of 600 mg) q21 × 4 cycles (arm B). After surgery, pts received trastuzumab q21 × 14 cycles using the same formulation (SC or IV) of the preoperative phase. The primary endpoint was the rate of stromal TILs (sTILs) on residual disease after surgery. Tumor biopsy and posttreatment surgical samples were centrally analyzed for TILs. Blood samples were also collected during NT for tumor-specific lymphocyte cell activity analysis. Feasibility, efficacy and safety were also evaluated. ClinicalTrials.gov: NCT03144947. Results: Between November 2016 and September 2017, according to an adaptive Simon9s two-stage optimal design, we enrolled 65 pts, of whom two were deemed ineligible for the study. Thus, 63 pts (31 in arm A and 32 in arm B) were assessed for the primary and secondary endpoints. The pathologic complete response (pCR; no invasive tumor in breast and axilla) rates were 64.5% (95% CI, 47-81) in arm A, and 59.4% (95% CI, 42-76) in arm B. The most common adverse events of grade 3 or higher were neutropenia (15 [48.4%] pts in arm A, and 11 [34.4%] in arm B), neurotoxicity (1 [3.2%], and 2 [6.2%], respectively), and diarrhea (1 [3.2%], and 1 [3.1%], respectively). There were no events of congestive heart failure. At surgery, 11 pts in arm A and 13 pts in arm B were evaluable for TIL analysis. The median value of sTILs (7.5%) on pre-treatment tumor biopsies was used as the cut-off value, and high sTIL levels were observed in 27.3% and in 46.1% of residual tumors after treatment arm A and B, respectively. There was a positive correlation between pretreatment sTILs and PD-L1 expression on stromal immune cells (Kendall’s τ =0.80). Interestingly, a significant inverse correlation was observed between PD-L1 expression on pretreatment sTILs and the T cell co-receptor CD3 expressed on posttreatment sTILs (Pearson’s ρ = -0.70). This finding was particularly evident in the arm B group (ρ = -0.85). Conclusions: NT with either SC or IV trastuzumab in combination with pertuzumab and chemotherapy had a significant effect on sTIL expression at surgery. In particular, the SC trastuzumab-based arm exerted the most relevant enrichment of sTILS in posttreatment residual tumors. These findings suggest a role for the SC administration of trastuzumab in determining favorable variations of host immune response parameters among pts with HER2-positive early BC who had residual disease after NT. Citation Format: Antonino Musolino, Stefania Gori, Elisabetta Cretella, Alessandra Marabese, Luigi Cavanna, Antonio Frassoldati, Giancarlo Bisagni, Chiara Casarini, Emilio Bria, Luisa Carbognin, Elena Fiorio, Alba A Brandes, Claudio Zamagni, Lorenzo Gianni, Alberto Zambelli, Filippo Montemurro, Michele Tognetto, Renata Todeschini, Giuseppe Maglietta, Gabriele Missale, Enrico M Silini. Phase II, open label, randomized, biomarker study of immune-mediated mechanism of action of neoadjuvant subcutaneous trastuzumab in patients with operable, locally advanced, or inflammatory HER2-positive breast cancer. ImmunHER trial on behalf of the Gruppo Oncologico Italiano di Ricerca Clinica (GOIRC) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-18-19.

Pertuzumab, a novel HER dimerization inhibitor, inhibits the growth of human NSCLC cells mediated by the HER3 signaling pathway

Abstract: 1510 Pertuzumab (Omnitarg, 2C4), a humanized anti-HER2 monoclonal antibody binding to a different HER2 epitope than Herceptin is an inhibitor of heterodimerization of the HER family, and shows potent antitumor activity against HER2-expressing breast and prostate cancer cell lines. In lung cancer cells the EGFR plays a crucial role in their biological behavior, but it is unclear whether pertuzumab inhibits the growth of the lung cancer cells mediated by ErbB. In this study, we focused on the antiproliferative effect of pertuzumab on non-small cell lung cancer (NSCLC) cells expressing different types of ErbB receptors in vitro, and we analyzed the mechanism of action of pertuzumab in the response to ligand-mediated ErbB receptor activation. The lung cancer 11_18 cell line overexpresses HER2 and HER3 but not EGFR, and its cell growth was stimulated by a HER3 ligand heregulin. Pertuzumab significantly inhibited the heregulin-stimulated cellular growth of the 11_18 cells. Heregulin-induced phosphorylation of HER3, MAPK, and Akt was inhibited in a dose-dependent manner by exposure of the 11_18 cells to pertuzumab. Heregulin-stimulated HER3 phosphorylation was also observed in the PC-9 and Ma-1 cell lines that overexpress HER3 and EGFR but their cell growth was neither stimulated by heregulin nor inhibited by pertuzumab. These results suggest that the cellular growth of lung cancer cells overexpressing HER3 but not EGFR is highly heregulin-dependent, and that these cells are sensitive to pertuzumab.

A locally advanced breast cancer that achieved pCR with pertuzumab, trastuzumab and docetaxel: Case report

Abstract: We herein report a case of locally advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer that achieved a pathological complete response (pCR) with pertuzumab, trastuzumab and docetaxel therapy. A 70-year-old female presented with an elastic hard mass, 5.0 cm in diameter with broad redness and edema of the skin in her right breast. Swollen lymph nodes were also recognized in the right axilla. The pathological diagnosis was invasive ductal carcinoma and its biological character was estrogen receptor (ER)-negative, progesterone receptor (PgR)-negative, HER2 3+ and Ki-67 index 60%. The patient was finally diagnosed with primary unresectable, locally advanced breast cancer and started on pertuzumab, trastuzumab and docetaxel combination therapy. The tumor subsequently reduced in size and, after 4 cycles of this therapy, she underwent surgery. The histopathological examination of the postoperative specimen showed pCR in both the primary tumor and axillary lymph nodes.

Tumor Infiltrating Lymphocytes and HER2-Positive Breast Cancer

Abstract: Prior findings suggest that high levels of tumor infiltrating lymphocytes (TILs) may confer improved prognosis and predict response to therapy in patients with breast cancer. To evaluate the anti-tumor effects of TILs in patients with HER2-positive, metastatic disease, investigators have now conducted an industry-funded, retrospective analysis of the CLEOPATRA study (N Engl J Med 2015 Feb 19; 372:724), which demonstrated a survival benefit of adding pertuzumab to trastuzumab and docetaxel in 808 women with HER2-positive metastatic …

HER dimerization inhibitors: developing pertuzumab as an anticancer agent in women's oncology.

Abstract: Background: Pertuzumab is a novel monoclonal antibody that blocks the dimerization domain of the human epidermal growth factor receptor (HER)-2/neu receptor, disabling its ability to form heterodimers with the other members of its family. Objective: We review the background and scientific rationale, but more specifically cover current clinical trial outcomes of pertuzumab in solid tumors, with an emphasis on the work completed in women's cancers. Methods: Clinical trial results published or presented at national meetings are included in this review. Results: Pertuzumab shows promising activity with trastuzumab in the treatment of metastatic breast cancer. The results in ovarian cancer have been limited thus far but a post hoc analysis of the results of a completed randomized Phase II trial of gemcitabine with or without pertuzumab suggests that low HER3 levels may mark a group of women who may benefit from the addition of pertuzumab to chemotherapy. Conclusions: The efficacy of pertuzumab independent of H...