Topic
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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TL;DR: Men1611 (Men) is an oral PI3K inhibitor active on the p110α mutant and wild type, β and γ isoforms, while sparing the δ as discussed by the authors .
Abstract:
Background: MEN1611 (MEN) is an oral PI3K inhibitor active on the p110α mutant and wild type, β and γ isoforms, while sparing the δ. B-PRECISE-01 is an open-label, 2-arm, phase 1b study investigating MEN1611 in combination with trastuzumab ± fulvestrant in patients with HER2 positive/PIK3CA mutated metastatic breast cancer (MBC). No dose-limiting toxicities were observed during the dose-escalation step and MEN1611 48 mg BID was selected as the recommended phase 2 dose (RP2D) for cohort expansion (CE). Methods: Eligible patients had HER2+/PIK3CA-mutated MBC and were treated with at least 2 prior lines of anti-HER2-based therapy in the advanced/metastatic setting including trastuzumab. Patients received MEN1611 + trastuzumab (MEN+T); hormone receptor positive (HR+) postmenopausal women received M+ T + fulvestrant (MEN+T+F). Recruitment was closed in December 2021. Pooled safety and efficacy data from the two subpopulations of CE are presented herein. Results: As of June 2022, 62 female patients were treated: 56 of them with MEN1611 48 mg BID (25 MEN+T and 31 MEN+T+F). Median age 55.5 years (range 34-78), 21% premenopausal, ECOG PS 0-1: 95.2%. Median metastatic regimens 4; 71.0% had prior pertuzumab and 91.9% had prior T-DM1. Common treatment-emergent adverse events (TEAEs, ≥20%) were diarrhea 66.1%, nausea 45.2%, hyperglycemia 43.6%, anemia 35.5%, asthenia 29.0%, decreased appetite 27.4%, rash 25.8%, aspartate aminotransferase increased 22.6%, vomiting 22.6%, and pyrexia 22.6%. Common TEAEs with CTCAE grade ≥3 (≥10%) were hyperglycemia (22.6%) and diarrhea (11.3%). Most treatment-related AEs (TRAEs) were reversible and manageable by supportive care. TEAEs leading to permanent treatment discontinuation occurred in 9 patients (14.5%), the only TEAE occurring in more than one patient was lipase increased (3.2%). TEAEs caused temporary treatment interruptions in 32 patients (51.6%), the most common being hyperglycemia (21.0%) and diarrhea (9.7%). TEAEs leading to dose reduction occurred in 14 patients (22.6%), the most common being diarrhea (6.5%), hyperglycemia (3.2%) and stomatitis (3.2%). Serious TRAEs were experienced by 12 patients (19.4%): hyperglycemia 6 patients, diarrhea 3 patients, anemia, general physical health deterioration, generalized edema, lipase increased, ketoacidosis and pneumonitis (1 patient each). In the efficacy-evaluable population at the RP2D (n=41) 14 patients (34.1%) showed partial response (MEN+T 5/15, MEN+T+F 9/26), 1 patient (2.4%) had a complete response (MEN+T 1/15) and 23 patients (56.1%) had stable disease (MEN+T 6/15, MEN+T+F 17/26) as best response. At the RP2D, the median (95% CI) overall survival (OS) was 21.9 (11.9, NE) months and the median (95% CI) progression free survival (PFS) 5.6 (3.7, 7.2) months. In the MEN+T group, the median OS was 11.9 (5.7, NE) months and median PFS 3.9 (2.3, 6.7) months. In the MEN+T+F group the median OS was 21.9 (16.9, NE) months and median PFS 5.7 (3.7, 11.5) months. Five patients continue on treatment. Conclusions: Updated results from B-PRECISE-01 demonstrated that MEN1611 combined with trastuzumab ± fulvestrant continued to show a manageable safety profile with encouraging anti-tumor activity and duration of response in heavily pre-treated patients with HER2+/PIK3CA-mutated advanced or metastatic breast cancer.
Citation Format: Martine Piccart, Audrey Hennequin, Manuel Ruiz Borrego, Santiago Escrivá-de-Romani, Anja Williams, Begoña Jiménez Rodríguez, Gianluca Del Conte, Sacha J. Howell, Michela Palleschi, Matteo Simonelli, Francois P. Duhoux, Diego Tosi, Bernard Doger de Speville Uribe, Yolanda Jerez Gilarranz, Pierfrancesco Tassone, Giuseppe Curigliano, Simon Waters, Philippe Aftimos, Hans Wildiers, Simona Scartoni, Bartomeu Piza Vallespir, Ram Charan Shankaraiah, Krzysztof Grzegorzewski, Nassir Habboubi. MEN1611, a PI3K inhibitor, combined with trastuzumab ± fulvestrant for HER2+/PIK3CA mutant advanced or metastatic breast cancer: updated safety and efficacy results from the ongoing phase 1b study (B-PRECISE-01) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD18-05.
1 citations
TL;DR: Wang et al. as discussed by the authors used CTCAE version 5.0 to evaluate the adverse reactions of trastuzumab (H) and pertuzumaab (P) combined with chemotherapy as neoadjuvant therapy in patients with HER2-positive breast cancer.
1 citations
TL;DR: This paper proposes schemes for management of the most common adverse events during the use of pertuzumab, including diarrhoea, neutropaenia and febrile neutrop aenia, and skin toxicities.
Abstract: Treatment outcomes of patients diagnosed with breast cancer with overexpression of the HER2 receptor have been significantly improved by the use of pertuzumab. Its use, however, is associated with the occurrence of various, more or less severe, adverse events. Some of them had already been observed in clinical practice during treatment with another monoclonal antibody directed against the HER2 receptor, trastuzumab. New toxicities, which occurred in a higher grade or significantly more frequently during treatment with pertuzumab are diarrhoea, neutropaenia and febrile neutropaenia, and skin toxicities. Their severity is generally acceptable, and proper management in the case of their occurrence is crucial for optimal causal treatment. This paper proposes schemes for management of the most common adverse events during the use of pertuzumab.
1 citations
TL;DR: TDM1 plus L and Nab-P therapy was well tolerated with noteworthy responses in all patients, including in PTEN low expressers, and can be evaluated as a surrogate for future studies.
Abstract: Background: We conducted a multicenter, randomized open-label phase II neoadjuvant study of trastuzumab-emtansine (T-DM1), Lapatinib (L) and Nab Paclitaxel (Nab-P) compared to standard of care (SOC) Paclitaxel (Pac), Trastuzumab (T), and Pertuzumab (P) in patients with HER2 over-expressed breast cancer. Methods: Patients in the experimental arm received a biologic window of targeted therapies alone for 6 weeks (T-DM1 and L) followed by T-DM1 3.0 mg/kg Q3W, L 750mg oral daily and Nab-P 80 mg/m2 weekly (QW) X 12 weeks. Patients in SOC arm received targeted therapies alone for 6 weeks (T and P) followed by Pac 80mg/m2QW, T 2mg/kg QW, and P 420mg Q3W X 12 weeks. The primary objective was to evaluate the proportion of patients with residual cancer burden (RCB) 0 or 1. Key secondary objectives included correlative assessments of PIK3CA mutations, PTEN expression, and HER2 subtypes which are being reported. Results: Thirty of the 33 enrolled patients were evaluable. Patient demographics were well balanced. HER2 subtypes and altered PIK3CA (low PTEN or PIK3CA mutations) pathway were not statistically different between both arms. We have previously reported that all patients achieved RCB 0 & I in the T-DM1, L and Nab-P arm, compared to SOC (100% vs. 62.5%, p 0.0035). In the SOC arm, the 6 week change in tumor size on breast MRI during targeted biologic window treatment is significantly different between the responders and non-responders based on two-sided Wilcoxon rank-sum test (p =0.0065). Consistent with literature, among ER positive patients treated with SOC, PTEN low expressers were less likely to respond (0%, 0 of 2) than PTEN high expressers (67%, 2 of 3). In the experimental arm, all patients responded regardless of PTEN. There was only 1 PIK3CA mutation on the experimental arm where all responded. Conclusions: TDM1 plus L and Nab-P therapy was well tolerated with noteworthy responses in all patients, including in PTEN low expressers. Change in tumor size at 6 weeks of biologic therapies was significant between responders and non-responders and can be evaluated as a surrogate for future studies. Citation Format: Creamer SL, Patel TA, Ensor JE, Rodriguez AA, Niravath PA, Darcourt JG, Kaklamani VG, Meisel JL, Li X, Zhao J, Kuhn JG, Rosato RR, Qian W, Belcheva A, Boone T, Chang J. Care 001: multi-center randomized open-label phase II trial of neoadjuvant trastuzumab emtansine (T-DM1) in combination with lapatinib and nab-paclitaxel compared with paclitaxel, trastuzumab and pertuzumab in HER2-neu over-expressed breast cancer patients (TEAL study) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-26.
1 citations
TL;DR: PerUSE is a phase IIIb, multicenter, open-label, single-arm study in pts with HER2-positive BC who have not been treated with systemic non-hormonal anticancer therapy for MBC to assess the safety and tolerability of P + H +-one of a choice of taxanes (T) as 1L therapy for pts with Her2- positive metastatic or locally advanced BC.
1 citations