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.

Adjuvant pertuzumab improves early breast cancer outcomes.

Abstract: New research suggests that in patients with operable HER2-positive breast cancer, treatment with pertuzumab, when given with trastuzumab and chemotherapy in the adjuvant setting, substantially improves invasivedisease-free survival when compared with treatment with placebo plus trastuzumab and chemotherapy. Like trastuzumab, pertuzumab is also a HER2 inhibitor. Results of previous studies have suggested that in patients with HER2-positive metastatic breast cancer, combination therapy with pertuzumab, trastuzumab, and docetaxel improved progression-free survival and overall survival. Gunter von Minckwitz (German Breast Group, Neu-Isenburg, Germany) and colleagues did a randomised, placebo-controlled, phase 3 trial in which patients with node-positive or node-negative HER2-positive early breast cancer were randomly assigned (1:1) to receive adjuvant pertuzumab (2400 patients) or placebo (2405 patients) in combination with chemotherapy and 1-year trastuzumab treatment. Disease recurrence occurred in 171 (7·1%) of 2400 in the pertuzumab group compared with 210 (8·7%) of 2405 in the placebo group (hazard ratio 0·81 [95% CI 0·66 to 1·00]; p=0·045). In the cohort of node-positive patients, 3-year invasivedisease–free survival was 92·0% in patients receiving pertuzumab compared with 90·2% in those receiving placebo (HR 0·77 [95% CI 0·62 to 0·96]; p=0·02), whereas in those with node-negative breast cancer, 3-year invasive-disease–free survival was 97·5% versus 98·4% (HR 1·13 [0·68 to 1·86]; p=0·64). The most common grade 3 or worse adverse events were neutropenia (385 [16·3%] patients in the pertuzumab groups vs 377 [15·7%] in the placebo group), febrile neutropenia (287 [12·1%] vs 266 [11·1%], and diarrhoea (232 [9·8%] vs 90 [3·7%]). According to von Minckwitz, the early findings of the study suggest that “we may be able to further improve outcomes for some women by adding a second HER2-targeted treatment, without increasing risk for serious side effects.” Luca Gianni (San Raffaele Cancer Centre, Milan, Italy) said, “As is, the data are in line with what was expected from the neoadjuvant trial NeoSphere, and score another point in favour of the role of neoadjuvant studies to predict outcome of large adjuvant trials.” However, he added, “the oncology community expected a larger effect and is concerned by the cost associated with a liberal prescription of pertuzumab.”

Abstract OT3-1-03: An open-label, multicentre, phase IIIb study with intravenous administration of pertuzumab, subcutaneous trastuzumab, and a taxane in patients with HER2-positive metastatic breast cancer (SAPPHIRE)

Abstract: Background: The primary goals of treatment for patients (pts) with metastatic breast cancer (mBC) are maximising survival and preserving the quality of life. Intravenous (IV) trastuzumab has proven clinical benefits in pts with human epidermal growth factor receptor 2 (HER2)-positive mBC. Pertuzumab also targets HER2 through an independent epitope to that of trastuzumab. Addition of pertuzumab to the established combination of trastuzumab and docetaxel has shown improved efficacy with acceptable toxicity in mBC (Swain et al. Lancet Oncol 2013;14:461-71); they are considered standard of care. Subcutaneous (SC) and IV trastuzumab formulations have shown comparable efficacy but SC administration is preferred by pts for reducing duration of clinic visits (Pivot, et al. Lancet Oncol 2013;14: 962–970). The combination of IV pertuzumab and SC trastuzumab has not been studied. The aim is to assess safety, tolerability, and efficacy of combining IV pertuzumab with SC trastuzumab and a taxane, as first-line therapy in pts with HER2-positive mBC. Trial Design: SAPPHIRE is an open-label, multicentre, Phase IIIb study. Pts will receive IV pertuzumab every 3 weeks with a loading dose of 840 mg and subsequent doses at 420 mg combined with SC trastuzumab at 600 mg/5 mL every 3 weeks and a taxane (docetaxel, paclitaxel, or nab-paclitaxel; regimen determined by the investigator). Treatment will continue until disease progression, unacceptable toxicity, or pts withdraw consent, whichever occurs first. The study is expected to run for 42 months. Eligibility: Pts aged ≥18 years old with histologically or cytologically confirmed HER2-positive [immunohistochemistry (IHC) positive at 3+ or in situ hybridisation-positive (ISH+)] mBC with at least one measurable lesion and/or non-measurable disease according RECIST version 1.1 and ECOG performance status (PS) 0-2 are eligible. Specific Aims: The primary objective is to assess the safety and tolerability of combining IV pertuzumab with SC trastuzumab and investigator’s choice taxane chemotherapy. The secondary objectives are to assess the efficacy of the first-line combination of pertuzumab, trastuzumab, and taxane chemotherapy and second-line treatments for mBC after disease progression. Statistical Methods: Primary safety analyses will report incidence and severity of adverse events (AEs)/serious AEs, AEs leading to premature discontinuation of study treatment and evidence of cardiac dysfunction. Secondary safety analyses will include exposure and duration of study treatment, ECOG PS and laboratory data. Secondary efficacy analyses will report the overall response rate, progression-free survival, event-free survival and overall survival. Continuous data will be summarised using mean, median, range, standard deviation, and standard error. Discrete data will be summarised using frequency counts and percentages. Time-to-event analyses will be based on Kaplan-Meier methodology. Accrual: The planned 50 pts will be recruited from 13 Australian Centres. The study started in December 2013 with 24 pts now enrolled. Clinicaltrials.gov#NCT02019277. Citation Format: Natasha Woodward, Richard H De Boer, Andrew Redfern, Vita Von Neumann-Cosel, Ronelle M Heath, Jane Beith. An open-label, multicentre, phase IIIb study with intravenous administration of pertuzumab, subcutaneous trastuzumab, and a taxane in patients with HER2-positive metastatic breast cancer (SAPPHIRE) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr OT3-1-03.

How safe is it to administer dual anti-HER2 block with pertuzumab and trastuzumab on a patient with life-threatening liver breast cancer metastasis?

Abstract: Aim: We report a case of a young woman who presented with HER2+ metastatic breast cancer and visceral crisis to asses safety and effectiveness of dual anti-HER2 plus chemotherapy. Patients & methods/materials & methods: At the time of advanced breast cancer diagnosis, the patient presented in scanty clinical condition with severe liver function tests elevation. First-line chemotherapy based on pertuzumab-trastuzumab plus weekly paclitaxel at 50% reduced dose due to liver dysfunction was administered. Results: Improvement and normalization of liver function tests and patient’s clinical condition was recorded in less than 2 months. Computed tomography revealed a partial remission of liver metastasis. Conclusions: Early initiation of standard HER2 target therapies outweigh the risks of toxicities and can be successfully used also in patients with life-threatening liver breast cancer metastasis.

4CPS-106 Safety of adjuvant trastuzumab emtansina for residual invasive HER2-positive early breast cancer

Abstract:

Background and importance

Trastuzumab-emtansine (T-DM1) is a treatment approved by the European Medicines Agency (EMA) in 2020 as a single agent for the adjuvant treatment of adult patients with HER2-positive early breast cancer (EBC) who have residual invasive disease, in the breast and/or lymph nodes, after neoadjuvant taxane-based and HER2-targeted therapy, in which it demostrated a significant improvement in invasive disease-free survival compared with trastuzumab.¹

Aim and objectives

Aim: to describe our experience with T-DM1 adjuvant for EBC treatment in real-world conditions (RWC). We analysed the T-DM1 safety profile and compared it with a pivotal trial (PT).¹

Material and methods

Retrospective study in a tertiary hospital. 100% patients with EBC treated with adjuvant T-DM1 between 2019 and 2021. Demographic data, basal Eastern Cooperative Oncology Group (ECOG), neoadjuvant therapy schedule, T-DM1 cycles received, adverse events (AEs), pegfilgastrim use, intentional dose delays, treatment interruptions and dose reductions were collected.

Results

29 patients received T-DM1. 100% women, average age 52 (range 27–75) years. 2/29 basal ECOG ≥1. 20/29 received neoadjuvant treatment based on doxorubicin (lyposomal or conventional) and cyclophosphamide followed by taxanes (19/20 paclitaxel, 1/20 docetaxel) with trastuzumab and pertuzumab. 24/29 presented toxicities to neoadjuvant treatment (15/29 thrombocytopenia). T-DM1 starting dose: 3.6 mg/kg/21 days in 28/29 patients. In 1/29, 3 mg/kg due to persistent thrombocytopenia. 10/29 receiving therapy at the time of the study. 8/19 received <14 cycles, 5/8 discontinued due to toxicities. 19/29 experienced ≥1 AE. Grade ≥3 thrombocytopenia was the most common (12/29), followed by increase in liver enzymes (ILE) (6/29), grade ≥2 neuropathy and grade ≥2 asthenia (5/29). 2/29 received pegfilgrastim. 3/29 patients had dose reduction (2/29 one, 1/29 two dose-level reductions). 7/29 experienced dose delays due to toxicities. Comparison RWC vs PT: any grade AE 65.5% vs 98.8%; grade ≥3 thrombocytopenia 41.4% vs 5.7%; grade ≥2 neuropathy 34.5% vs 1.5%; ILE 20.7% vs 5.6%; discontinuation due to toxicities 17.2% vs 18.0%; dose reductions 10.3% vs 10.4%. Dose delays and reduced initial dose were not considered in the PT.

Conclusion and relevance

Safety profile of T-DM1 in RWC is consistent with the PT results. Overall AEs in RCW were lower than in the PT. Grade ≥2 AEs were higher in RWC but not related to increased discontinuations or dose reductions. Our results should be interpreted with caution due to the sample size.

References and/or acknowledgements

1. von Minckwitz G, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med 2019;380(7):617–628.

Conflict of interest

No conflict of interest

Tolerability and effectiveness of pertuzumab-containing neoadjuvant (NA) regimens vs. AC-TH for HER2-positive (+) localized breast cancer (BC).

Abstract: 586Background: Based on improvement in pathologic complete response (pCR) in the NEOSPHERE and TRYPHAENA studies, the FDA approved NA pertuzumab with trastuzumab (HP) and chemotherapy for HER2+ localized BC. These studies demonstrated higher pCR rate with THP (docetaxel+HP) as compared to TH (pCR 45.8 vs. 29%), and high pCR rates with FEC (5-fluorouracil, epirubicin and cyclophosphamide)-THP (pCR 54.7%) and TCHP (docetaxel, carboplatin+HP, pCR 63.6%). However, in the US, doxorubicin/cyclophosphamide (AC) given in a dose-dense fashion is favored over FEC, though there is no data comparing AC-THP with AC-TH or TCHP. Here we report outcomes for pertuzumab-containing NA regimens and compare effectiveness and toxicity with AC-TH. Methods: We reviewed patients treated at our institution with either a NA pertuzumab-containing regimen or AC-TH from 2011 to 2015 for HER2+ BC. pCR was defined as ypT0/is ypN0. Fisher’s exact test and logistic regression analysis were used for statistical analysis. Results: Eighty pa...